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synergism between aphidicolin and adenoviruses in the induction of breaks at fragile sites on human chromosomes.infection of human embryonic kidney cells with adenoviruses results in the induction of gaps and breaks in cell chromosomes. with adenovirus type 12, cytogenetic damage is known to occur primarily at fragile sites on chromosomes 1 and 17. we have mapped adenovirus type 5-induced breaks and have observed that, although they occur on all chromosomes, they are localized primarily on bands where fragile sites have been mapped. the susceptibility of fragile sites to adenovirus led us to investigate t ...19911648440
cellular hypersensitivity to a synthetic dodecapeptide derived from human adenovirus 12 which resembles a sequence of a-gliadin in patients with coeliac disease.the human intestinal adenovirus serotype 12 (ad12) may be implicated in the pathogenesis of coeliac disease by virtue of immunological cross reactivity between epitopes shared by its early region e1b protein and a-gliadin. in the present study a synthetic dodecapeptide from the corresponding viral epitope (ad12e1b, residues 384-395) was tested for its effect on peripheral blood mononuclear cells from 22 treated and eight untreated patients with coeliac disease, 22 healthy subjects, 11 patients w ...19901696236
spreading of dna methylation across integrated foreign (adenovirus type 12) genomes in mammalian cells.the establishment of de novo-generated patterns of dna methylation is characterized by the gradual spreading of dna methylation (i. kuhlmann and w. doerfler, j. virol. 47:631-636, 1983; m. toth, u. lichtenberg, and w. doerfler, proc. natl. acad. sci. usa 86:3728-3732, 1989; m. toth, u. müller, and w. doerfler j. mol. biol. 214:673-683, 1990). we have used integrated adenovirus type 12 (ad12) genomes in hamster tumor cells as a model system to study the mechanism of de novo dna methylation. ad12 ...19911712860
identification of reactive synthetic gliadin peptides specific for coeliac disease.gluten intolerance (coeliac disease) is characterised by the development of a small intestinal lesion following exposure to the gliadin fraction after consumption of wheat and related cereals. cellular immune mechanisms are thought to be responsible for gliadin toxicity, but the toxic sequence/s within gliadin have not been clearly established. a panel of synthetic gliadin peptides was tested using peripheral blood mononuclear cells from coeliac patients and two assays for cell-mediated immunity ...19911720424
changes in nf-kappa b and isgf3 dna binding activities are responsible for differences in mhc and beta-ifn gene expression in ad5- versus ad12-transformed cells.changes in mhc class i expression are frequently observed in tumors, which represents at least one mechanism by which tumor cells escape immune surveillance. mhc class i expression is often suppressed in type 12 adenovirus (ad12)-transformed rodent cells, but is highly induced in ad5-transformed cells. this difference helps to explain why ad12 but not ad5 can induce tumors in immunocompetent syngeneic rats. in this report we demonstrate that only ad5- but not ad12-transformed rodent fibroblasts ...19911756724
genomic dna analysis of rat retinal tumor induced by adenovirus type 12.to elucidate the pathogenesis of human retinoblastoma, we investigated the genomic expression in retinal tumors induced by human adenovirus type 12 in rats, using various dna probes. seven rats received a single intraocular inoculation of concentrated virus fluid within 24 hours after birth. intravitreous tumors were induced in two out of seven animals (28.5%) within 30 to 64 days after the inoculation. a remarkably uniform histologic feature, i.e., neuroblastic cells in association with homer-w ...19911785341
viral transformation increases vitamin k-dependent gamma-carboxylation of glutamate.mammalian cells contain a microsomal vitamin k-dependent carboxylase activity which catalyzes the gamma-carboxylation of glutamate. while most cells have a limited ability to fully gamma-carboxylate proteins, it has been suggested that the ability of transformed cells to perform this complex post-translational modification may play a role in tumor biology. in this study, we examined the effect of transformation by adenovirus oncogenes on the ability of cells to efficiently gamma-carboxylate a vi ...19911824587
transcription stimulation of the adenovirus type-12 e1a gene in vitro by a novel factor bound to a region adjacent to a tata box.the e1a gene of adenovirus (ad) type-12 possesses two transcription start points (tsp) separated by 139 nucleotides (nt). we previously found that transcription from a tsp distal to the coding region is preferentially stimulated in a cell-free reaction by nuclear factor i (nf-i) bound to a region near the left end of the virus genome. we report here on the identification of a cis-acting dna region and a trans-acting factor for transcription initiated at the proximal tsp of the ad12 e1a gene. a d ...19911837279
differential regulation of junb and jund by adenovirus type 5 and 12 e1a proteins.the genes of the jun family encode components of the tpa-inducible transcription factor ap-1. these genes are induced by a wide variety of extracellular stimuli, such as growth factors, phorbol esters and activators of protein kinase a. we have previously shown that the adenovirus type 5 e1a protein (e1a5) induces c-jun and junb expression in a number of different cell types. in this paper we show that the third member of the jun family, jund, is also strongly induced by e1a5. multiple sequences ...19911837351
the use of beta-galactosidase fusion proteins encoding the early region 1 transforming proteins of adenovirus type 12 to examine the humoral response in tumour-bearing animals.sera from 26 rats bearing tumours induced by wild-type (wt) and mutant human adenovirus type 12 (ad12), or by cells transformed with these viruses, were analysed for antibodies against the early region 1 (e1) transforming proteins. six ad12-beta-galactosidase fusion proteins encoding different regions of the ad12 e1 proteins were constructed. the sera from the tumour-bearing animals reacted most strongly with the fusion protein encoding the n terminus of the e1a protein. tumour-bearing rats expo ...19911849978
suppression of murine leukemia virus-mediated 3y1 cell fusion by expression of mouse mhc class i.rat 3y1 fibroblasts transformed by adenovirus type 12 or its e1a gene formed syncytia by cocultivation with friend murine leukemia virus (mulv)-producing cells. on the other hand, parental 3y1 cells and those derivatives induced by other tumor viruses or chemical carcinogen showed no mulv-mediated syncytium formation [n. momozaki et al. (1990) arch. virol. 115: 123-126]. the expression of major histocompatibility complex (mhc) class i mrna and antigens was significantly reduced in these ad12- an ...19911863224
different chemosensitivities of rat 3y1 fibroblasts transformed by various agents in vitro.alterations of chemosensitivities associated with transformation of rat 3y1 fibroblasts were compared among various agents, including either adenovirus type 12 (ad12-3y1), the e1a region of adenovirus type 12 (e1a-3y1), mouse polyoma virus (py-3y1), simian virus 40 (sv-3y1), rous avian sarcoma virus (sr-3y1), plasmid dna carrying v-ha-ras oncogene (hr-3y1), or n-methyl-n'-nitro-n-nitrosoguanidine (ng-3y1), with untransformed 3y1 fibroblasts, using a semiautomated non-clonogenic mtt assay. ic50 v ...19911888164
transcriptional and posttranscriptional regulation of class i major histocompatibility complex genes following transformation with human adenoviruses.transformation of rodent cells by human adenoviruses is a well-established model system for studying the expression, regulation, and function of class i antigens. in this report, we demonstrate that the highly oncogenic adenovirus type 12 operates at the transcriptional and posttranscriptional levels in regulating the activity of major histocompatibility complex class i genes and products in transformed cells. adenovirus type 12 suppresses the cell surface expression of class i antigens in most ...19911895404
formation in vitro of the ptp-dcmp initiation complex of human adenovirus type 12.we report the covalent addition of [32p]dcmp to a protein from group a adenovirus 12 (ad12)-infected human (kb) cells in vitro, using crude extracts. synthesis of the 60k protein-dcmp complex required a dna template containing a terminally located adenovirus replication origin; the protein-dcmp bond was alkali-labile but acid-stable. we therefore conclude that this product is the ad12 terminal protein precursor (ptp)-dcmp initiation complex for dna replication. synthesis of ad12 ptp-dcmp was spe ...19911993880
identification of sequences responsible for positive and negative regulation by e1a in the promoter of h-2kbm1 class i mhc gene.the mechanism of transcriptional regulation of the h-2kbm1 major histocompatibility complex (mhc) class i gene by adenovirus type 12 e1a (ad12-e1a) was studied in transfected rat embryonal fibroblasts. results of long-term expression of the chloramphenicol acetyl transferase (cat) gene placed under the control of the 5'-flanking region of the mouse mhc class i gene. h-2kbm1, and the results of nuclear run-on transcription assays, yield evidence for both positive and negative regulation of h-2kbm ...19902136829
adenovirus type 12 tumour antigen synthesis differs during infection of permissive and non-permissive cells.synthesis of the adenovirus type 12 e1a and e1b tumour antigens was compared in productively infected human (kb) cells and in abortively infected baby hamster kidney (bhk) cells. by the use of anti-peptide antibodies, the e1a tumour antigens were easily detectable in infected kb extracts as early as 6 h post-infection, but were not detectable in infected bhk extracts until 12 h post-infection. the level of e1a tumour antigens detected in bhk extracts was 10 to 15% of that detected in kb extracts ...19902138209
induction of gd3 ganglioside by adenovirus e1a gene 13s- and 12s-mrna products in rat 3y1 cells.the effect of the expression of the human adenovirus type 12 e1a gene on ganglioside composition of rat 3y1 cells was investigated using cell lines established by introduction of recombinant vector dna containing the e1a 13s- or 12s-mrna cdna placed downstream of the hormone-inducible promoter of mouse mammary tumor virus. ganglioside gd3 was newly detected after switching on of either 13s- or 12s-mrna cdna by addition of dexamethasone. a kinetic study indicated that gd3 was expressed 8 h after ...19902144522
differential requirement for adenovirus type 12 e1a gene products in oncogenic transformation.during the early period of infection, adenovirus type 12 e1a gene is expressed as overlapping, spliced mrnas of 12 and 13s, which encode in-frame proteins of 235 and 266 amino acid residues (235r and 266r), respectively. to define the functions of these related products in the infection of human cells and transformation of rodent cells, we created single t-to-c transitions at the second base of each mrna intron which specifically prevent splicing of the respective mrnas. mutant pm712 expresses o ...19902144595
cloning of adenovirus type 12 e1 genes into a retroviral vector and their differential splicing in mouse cells.early region 1 (e1) of adenovirus type 12 (ad12) genome is able to transform nonpermissive primary rodent cells in vivo and in vitro. to analyse the role of the e1a gene products alone or in connection with the 58-kda protein encoded by e1b during oncogenic transformation, we have cloned genomic fragments of both subregions into the retroviral vector, pzip-neosv(x)1. both constructs are expressed in mouse 3t3 cells, but, in contrast to e1b, the amount of genomic retroviral rna carrying e1a-speci ...19902145196
isolation and characterization of novel adenovirus type 12 e1a mrnas by cdna pcr technique.the technique of cdna polymerase chain reaction was used to study the heterogeneity of adenovirus type 12 early region 1a mrnas in infected and transformed cells. in addition to 13 s and 12 s mrnas, three transcripts of 10 s, 9.5 s, and 9 s could be isolated from infected hela cells. a fourth transcript of 11 s was found in transformed cells. the 9 s mrna is generated by removing one intron (nucleotide (nt) 589 to nt 1143) from the rna precursor. for the 11 s and 10 s mrnas the primary transcrip ...19902146800
a mitigator sequence in the downstream region of the major late promoter of adenovirus type 12 dna.human adenovirus type 12 (ad12) replicates in permissive human host cells, but undergoes an abortive infection cycle in non-permissive hamster cells. ad12 dna cannot replicate and late viral genes are not expressed in hamster cells, whereas most of the early viral mrnas are synthesized. we have shown previously that the major late promoter of ad12 dna (ad12 mlp; nucleotides -228 to +435 relative to nucleotide +1 as the site of transcriptional initiation) does not function in uninfected or in ad1 ...19902158446
activation of retrovirus in transgenic mice: association with development of olfactory neuroblastoma.a line of transgenic mice that express the human adenovirus type 12 e1a and e1b genes under the regulatory control of the mouse mammary tumor virus long terminal repeat was studied. mice from this line develop olfactory neuroblastomas at approximately 6 months of age. large numbers of type c retrovirus (ecotropic murine leukemia virus) particles were found in the tumor rosettes. no similar examples of virus activation were identified in tumors from other transgenic experiments. examination of sp ...19902164606
selective syncytium formation by murine leukemia virus in rat 3y1 fibroblasts transformed by adenovirus type 12 or its e1a gene.3y1 rat fibroblasts transformed by adenovirus type 12 or by its e1a gene formed syncytia when cocultivated with the friend as well as other ecotropic murine leukemia-virus-producing cells. in contrast, the parental 3y1 cells and those transformed by other tumor viruses or by a chemical carcinogen exhibited no syncytium formation.19902174230
alteration in expression of smooth muscle alpha-actin associated with transformation of rat 3y1 cells.expression of actin was examined in a cultured rat embryonic cell line 3y1 and transformed cell lines that originated from 3y1. an alpha-actin in addition to cytoplasmic beta- and gamma-actins was detected in 3y1 by two-dimensional gel electrophoresis. this alpha-actin was hardly detected at all in the transformants induced by rous sarcoma virus, v-h-ras oncogene or adenovirus type 12, while the alpha-actin was retained in the transformed cell lines induced by n-methyl-n'-nitro-n-nitrosoguanidin ...19902283360
parental age and seasonal variation in the births of children with sporadic retinoblastoma: a mutation-epidemiologic study.statistical analysis of parental age data from 225 sporadic cases of bilateral retinoblastoma, plus ten sporadic cases of chromosome deletion or translocation involving 13q14 that was identified as of paternal origin, revealed no evidence of paternal or maternal age effect. parental exposure to ionizing radiation or chemical mutagens, the effect of which is accumulated with advancing age, does not seem to play a major role in the production of germinal mutations at the responsible (rb) locus. fu ...19902298450
chromosomal damage induced by human adenovirus type 12 requires expression of the e1b 55-kilodalton viral protein.infection of human embryonic kidney cells with adenovirus type 12 results in the induction of damage at specific (17q21-22, 1p36, 1q21, and 1q42-43) and random sites in the cellular chromosomes. a previous study by durnam et al. (d. m. durnam, p. p. smith, j. c. menninger, and j. k. mcdougall, cancer cells 4:349-354, 1986) indicated that the expression of viral early region 1 (e1) is sufficient for the induction of damage at band 17q21-22. in the present report we used an adenovirus type 12-aden ...19902325204
extracts of hamster cells abortively infected with human adenovirus type 12 are competent to support initiation of viral dna replication.baby hamster kidney (bhk-21) cells do not allow replication of human adenovirus type 12 (ad12) dna during abortive infection by this virus. however, we have determined that crude extracts of bhk-21 cells abortively infected with ad12 support in vitro the initiation reaction of ad12 dna replication. synthesis of the ad12 ptp-dcmp initiation complex by bhk extracts is two- to five-fold less than when crude infected human (kb) cell extracts are used in the reaction. combining infected kb cytoplasmi ...19902330676
nucleotide sequence of the right 10% of adenovirus type 12 dna encoding the entire region e4. 19902349112
confluent balb/c 3t3 cells monolayer provides selective and efficient growth of neoplastic cells.in an attempt to further characterize non-irradiated contact-inhibited confluent monolayer of balb/c 3t3 cells (= contact-sensitive plates; csp) as substrata for in vitro drug sensitivity testing, we compared the efficiency of colony formation with panels of cell lines on csp with that on plastic dishes or in agar. tumorigenicity in athymic nude mice was also examined. we found that: (1) hela cells, 2 esophageal cancer lines, rat 3y1 fibroblasts transformed by either adenovirus type 12, mouse po ...19902379137
neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation.efforts to investigate the progression of events that cause human cells to become neoplastic in response to ionizing radiation have been aided by the development of tissue culture systems of epithelial cells. in the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus type 12 and simian virus 40 have been transformed by exposure to x-ray irradiation. such transformants showed morphological alterations, formed colonies in soft agar, and induced carcinomas when tr ...19902405395
analysis of pp60c-src protein kinase activity in hamster embryo cells transformed by simian virus 40, human adenoviruses, and bovine papillomavirus 1.we have examined the effect of dna tumor virus transformation of primary hamster embryo cells on the tyrosyl kinase activity of pp60c-src. our present study demonstrates that some clones of hamster embryo cells transformed by simian virus 40, adenovirus type 2, adenovirus type 12, or bovine papillomavirus 1 can possess elevated pp60c-src kinase activity when compared with normal hamster embryo cells. however, other clones of hamster embryo cells transformed by these same viruses were found to ha ...19862416954
structural characterization of neovascularization in adenovirus-12-induced retinal tumor.in order to elucidate a relationship between newly formed micro-blood vessels in retinal tumor and blood-retina barrier, we studied light and electron microscopic and immunohistochemical findings of newly-formed micro-blood vessels in human adenovirus 12-induced retinoblastoma-like tumors in rats. in contrast to other experimentally induced tumors of the central nervous system, there was no evidence of formation of weibel-palade bodies and endothelial gaps in this experimental model of retinobla ...19872441568
analysis of an adenovirus type 12 temperature-sensitive mutant defective in interferon induction.among several temperature sensitive mutants of human adenovirus type 12 (ad12), h12ts15 was found to be defective in induction of interferon (ifn) in chick cells. this mutant was characterized as late mutant which synthesized defective iii.a and penton-base antigens and failed to assemble into infectious particles at restrictive temperature. moreover, its defect was manifested at permissive temperature, at which defective particles were readily formed. temperature shift experiments revealed that ...19882459945
a cell mutant that exhibits temperature-dependent sensitivity to transformation by various oncogenes.we previously isolated a fisher rat fibroblast mutant, b812, that has the unique property of temperature-dependent transformation by various oncogenic retroviruses. at the permissive temperature (35 degrees c), this mutant was sensitive to oncogenic transformation and formed foci on a dish at the same frequency as did the parental fibroblast cell line. when kirsten murine sarcoma virus (ki-msv) was applied to the cells, the frequency of focus formation decreased more than 25-fold at the nonpermi ...19892479832
regulation of major histocompatibility class i gene expression at the level of transcription in highly oncogenic adenovirus transformed rat cells.highly oncogenic adenovirus type 12 (ad12) transformed rat cells contain decreased levels of cytoplasmic and nuclear major histocompatibility (mhc) class i transcripts, a process dependent on the presence of the ad12 e1a oncogene. here we show that the reduction in mhc expression is due at least in part to a decreased rate of initiation of transcription of mhc class i genes. gamma-interferon treatment of ad12 transformed cells causes an elevation in steady-state levels of cytoplasmic mhc class i ...19882484015
modulation of major histocompatibility complex (mhc) class i genes in adenovirus 12 transformed cells: interferon-gamma increases class i expression by a mechanism that circumvents e1a induced-repression and tumor necrosis factor enhances the effect of interferon-gamma.the protein products of the e1a gene of adenovirus type-12 (ad12) block transcription of major histocompatibility (mhc) class i genes in both rodent and human transformed cells and interferon-gamma (ifn-gamma) is able to override this repression. although ifn-gamma is known to stimulate class i transcription, we investigated whether its dominance over e1a repression could alternatively result from the ability of this cytokine to induce antiviral mechanisms. we show that this is not so, since the ...19892521704
chromatin structure and levels of expression and dna methylation in the e3 region of chromosomally integrated adenovirus type 12 dna.integrated adenovirus type 12 (ad12) genes in ad12-transformed cell lines were investigated for chromatin structure, expression levels and states of dna methylation. the e3 region in the ad12-transformed cell line ha12/7 is hypermethylated and not expressed. the same region in the ad12-transformed hamster cell lines t637 and a2497-3 is transcribed and undermethylated (kruczek, i. and doerfler, w. (1982) embo j. 1, 409-414). there was no significant difference in the dnase i sensitivity of the e3 ...19892522012
genome structure of adenovirus 12 host range mutants adapted to growth in simian vero cells.mutants of adenovirus type 12 adapted to growth in vero cells were studied by restriction enzyme and sequence analysis. plaque-purified mutants were isolated either after long-term passage of the virus in vero cells (cs-1, cl-1) or from vero cells transfected with viral dna (11-g, 12-k). the plaque-forming activity of these mutants was equal or even slightly higher in vero cells than in hela cells, whereas the activity of wild-type virus in hela cells exceeded that in vero cells by about one to ...19892524454
adenovirus type 12 e1a down regulates expression of a transgene under control of a major histocompatibility complex class i promoter: evidence for transcriptional control.the e1 region of human adenovirus type 12 (ad12 e1) represses the expression of major histocompatibility complex (mhc) class i genes in transformed primary rodent cells. conflicting results have been reported as to whether this e1a-mediated repression occurs at a transcriptional or a posttranscriptional level. in the present study, we show that in ad12 e1-transformed primary baby mouse kidney cells from transgenic mice harboring the human growth hormone gene under control of an h-2k promoter bot ...19892527313
mechanism of selective killing by dilinoleoylglycerol of cells transformed by the e1a gene of adenovirus type 12.rat 3y1 fibroblasts transformed by the e1a gene of adenovirus type 12 (e1a-3y1 cells) are highly sensitive to the cell-killing effect of 1,3-dilinoleoylglycerol (dlg) administered in a culture medium, whereas the parental 3y1 cells are less sensitive (h. shimura et al., cancer res., 48: 578-583, 1988). the selective cytotoxicity of dlg to e1a-3y1 cells was markedly reduced by the simultaneous administration of nonspecific antioxidants such as vitamin e, butylated hydroxytoluene, and ascorbic aci ...19892529026
adenovirus infection retards ribosomal rna processing.eight hours after infection of kb cells with adenovirus type 12, the rate of conversion from the 32s ribosomal rna (rrna) precursor to mature 28s and 5.8s rrna decreased. an additional rna species was detected, which appears to be novel, on the basis of its estimated size (about 6.5 kilobases) and its high level of radiolabeling early after infection at low multiplicity.19892536036
embryonal neuroepithelial tumors induced by human adenovirus type 12 in rodents. 1. tumor induction in the peripheral nervous system.human adenovirus type 12 (ad 12) was inoculated intraperitoneally, intrapleurally, intramuscularly or subcutaneously into newborn rodents. tumors developed preferentially in the peritoneal cavities in 93.9% of the hamsters and 82.6% of the mice, but none in rats; in contrast to the high incidence of brain tumors in rats when the virus is injected intracranially. serial section of peritoneal tissues and muscle of hamsters revealed multicentric microtumors with a close relation to peripheral nerve ...19892538040
recombination in hamster cell nuclear extracts between adenovirus type 12 dna and two hamster preinsertion sequences.a cell-free system of nuclear extracts from bhk21 cells has been developed to catalyse recombination in vitro between the dna of adenovirus type 12 (ad12) and two different hamster preinsertion sequences. the pbr322 cloned 1768 bp fragment p7 and the 3.1 kbp fragment p16 from bhk21 hamster dna had previously been identified as the preinsertion sites corresponding to the junctions between ad12 dna and hamster dna in cell line clac1 and in the ad12-induced tumour t1111(2), respectively. preinserti ...19892542024
transgenic mouse model for human gastric carcinoma.to understand the pathogenesis that may be induced by human adenovirus type 12 (ad12), we have generated transgenic mice carrying the ad12 early region 1 under control of the mouse mammary tumor virus long terminal repeat. eleven of 11 male founder mice, but only 2 of 12 females, died between 3 to 4 mo of age. death was associated with presence of tumors at or near the squamocolumnar junction of the stomach. microscopically, these multifocal tumors appeared to arise from hyperplastic epithelium ...19892546160
selective killing of transformed fibroblasts by combined treatment with cycloheximide and aphidicolin.the possibility of selective killing of transformed cells in a mixed population of untransformed and transformed cells was examined using a cell culture system of rat 3y1 fibroblasts (parental 3y1 cells, 3y1 cells transformed with either sv40, polyoma virus, rous avian sarcoma virus, e1a gene of adenovirus type 12, or h-v-ras oncogene). the principle of the selective killing is as follows. under suboptimal culture conditions, untransformed cells are inhibited from progressing through g1 phase an ...19892546909
embryonal neuroepithelial tumors induced by human adenovirus type 12 in rodents. 2. tumor induction in the central nervous system.intracranial inoculation with human adenovirus type 12 (ad12) induced tumors multicentrically in the brain and spinal cord of 37.2% of hamsters, 30.2% of mice, and in the brains of 91.0% of rats. brain tumors developed preferentially at the olfactory bulb, lateral ventricular horns, tapetum region, and ventral and dorso-caudal aspects of the fourth ventricle. in the spinal cord, tumor developed on the dorsal aspect and, in hamsters, at the root of the cauda equina. microtumors were found almost ...19892548365
frequency of cell transformation by the small dna tumor viruses: infection of proliferating cells and quiescent cells.small dna-containing tumor viruses (simian virus 40, mouse polyoma-virus, and adenoviruses) malignantly transform fibroblasts of the susceptible rodents. fibroblasts can exist, in vitro and in vivo, in either of the two states: the proliferating state or the quiescent state. in the present study, we examined whether the state of fibroblasts at the time of exposure to these dna viruses affects the frequency of transformation. dense-focus formation in monolayer culture of rat 3y1 fibroblasts was u ...19892550745
heat- or stress-inducible transformation-associated cell surface antigen on the activated h-ras oncogene-transfected rat fibroblast.a wka rat fetus fibroblast (wfb) was transfected by several oncogenes including ejras (activated h-ras), polyoma middle t (pymt), v-src, c-myc, and adenovirus type 12 e1a-e1b. we analyzed the expression of the transformation-associated cell surface antigens on wfb by developing monoclonal antibodies. one of the wfb transformation-associated cell surface antigens, recognized by monoclonal antibody 067, was constitutively expressed only on two (w31 and w70) of ten wfb-ejras-transformed clones. thi ...19892555046
suppression of mhc class i rna in highly oncogenic cells occurs at the level of transcription initiation.the oncogenic potential of some transformed cell lines has been shown in animal tumor models to be the direct result of mhc class i mrna suppression. rodent cells established with the highly oncogenic human adenovirus type 12 exhibit greatly reduced levels of class i ag compared with cells derived with the nononcogenic adenovirus type 5. by using seven independently derived adenovirus-transformed cell lines, we have investigated the mechanism responsible for down-regulation of class i rna expres ...19892685121
the expression of heat shock protein hsp27 and a complexed 22-kilodalton protein is inversely correlated with oncogenicity of adenovirus-transformed cells.we isolated a monoclonal antibody that immunoprecipitated two proteins of 22 and 27 kilodaltons (kda) from nononcogenic adenovirus type 5 early region 1 (e1)-transformed rat cells but not from oncogenic adenovirus type 12 e1-transformed rat cells. in a variety of adenovirus-transformed cells including cells transformed by e1a and the c-h-ras oncogene, we found a perfect, inverse correlation between the presence of these two proteins and the oncogenicity of these cells in syngeneic immunocompeten ...19892746733
defect of adenovirus type 12 replication in hamster cells: absence of transcription of viral virus-associated and l1 rnas.the nonpermissive interaction of hamster cells with human adenovirus type 12 (ad12) is characterized by a total block of ad12 dna replication and late transcription, whereas most of the early functions of ad12 dna can be transcribed. ad2 can replicate in hamster cells. the replication and late transcription defects of ad12 dna can be complemented to a certain extent by the e1b functions of ad2 dna. this complementation fails, however, to lead to the synthesis of the late ad12 proteins and to the ...19892746738
simian adenovirus type 7 (sa-7) induces tumours of nerve-supporting or paraneural cell origin in newborn hamsters.simian adenovirus type 7 (sa-7) was found to induce tumours originating from nerve-supporting or paraneural cells in newborn hamsters, regardless of injection site or tissues. sa-7 induces glioblastomas characterized by definite localization (subependymal regions) and its main cell type, bipolar spongioblast-like cells, in the brain of hamsters inoculated as newborns. when the eyes of newborn hamsters were directly inoculated, sa-7 failed to induce retinoblastoma (0/27), but retro or peri-bulbar ...19892765394
arrangement and expression of integrated adenovirus type 12 dna in the transformed hamster cell line ha12/7: amplification of ad12 and c-myc dnas and evidence for hybrid viral-cellular transcripts.in the genome of the adenovirus type 12 (ad12)-transformed hamster cell line ha12/7 about three copies of the viral dna are fixed by integration. the results of blot-hybridization, molecular cloning, and nucleotide sequencing experiments suggest a model for the arrangement of ad12 dna molecules in which the left hand terminus of one of the ad12 dna copies is linked to unique hamster dna. the right hand end of this dna molecule is fused to an inverted copy of a left terminal approximately 4.3 kb ...19892773593
analysis of retinoblastoma for human adenovirus and human jc virus genome integration.human adenovirus groups a and b have an oncogenic potential in newborn rodents. especially, adenovirus type 12 is known to induce retinoblastoma-like tumor in baboons and transform human embryo retinoblast cells in vitro. human jc virus is also known to produce a variety of tumors in newborn rodents, including retinoblastoma-like tumor. in this experiment, cell dnas of human retinoblastomas were assayed for each of the transforming gene sequences of adenovirus groups a, b, c, d and e and for jc ...19872822987
viral infections in pediatric bone marrow transplant patients.the records of 96 pediatric patients with aplastic anemia or a malignancy who underwent bone marrow transplantation between 1979 and 1986 at the children's hospital of philadelphia were reviewed for laboratory evidence of viral infections. the most common viral diseases identified were herpes simplex virus (hsv), cytomegalovirus and adenoviruses, which were found in 19 (20%), 17 (18) and 17 (18) patients, respectively. hsv was more common in patients with than without graft vs. host disease (gvh ...19882830586
viral gene inhibition of class i major histocompatibility antigen expression: not a general mechanism governing the tumorigenicity of adenovirus type 2-, adenovirus type 12-, and simian virus 40-transformed syrian hamster cells.the association between the level of class i major histocompatibility (mhc) antigen expression and the tumorigenic phenotype was determined for cells from a series of 15 lines of adenovirus type 2 (ad2)-, ad12-, and simian virus 40 (sv40)-transformed hamster cells and 16 lines of cells established from hamster tumors induced by sv40 mutants. these cells range from nontumorigenic to highly tumorigenic in both syngeneic and allogeneic adult hamsters. the ad2-transformed cells--cells that were nont ...19882839700
influence of the deprivation of a single amino acid on cellular proliferation and survival in rat 3y1 fibroblasts and their derivatives transformed by a wide variety of agents.we compared proliferation and survival of various syngeneic transformed cell lines under conditions of depletion of 15 amino acids in dulbecco-eagle's medium. we used a normal fibroblast line 3y1 and 22 transformed sublines of 3y1 which had been induced by one of seven transforming agents--simian virus 40, mouse polyomavirus, adenovirus type 12, e1a gene of adenovirus type 12, cdna of harvey murine sarcoma virus, rous sarcoma virus, or n-methyl-n'-nitro-n-nitrosoguanidine. unlike other untransfo ...19882844831
the high sensitivity of cells transformed by e1a gene of adenovirus type 12 to diacylglycerol-mediated cell killing.viability of rat 3y1 fibroblasts transformed by adenovirus type 12 (ad12) was markedly impaired by the administration of dilinoleoylglycerol (dlg) to the culture medium. to identify the gene(s) of ad12 responsible for the high sensitivity to dlg, we established several transformed sublines of 3y1 induced by the viral e1a gene or by the mutants of ad12 which have mutations in the e1a region. all of the transformed sublines of 3y1 expressing either the 12s or the 13s message from the e1a region we ...19892920374
an insertion mutation in the adenovirus type 12 early region 1a 13s mrna unique region.an adenovirus type 12 mutant, in203s, was constructed to contain an insertion of two amino acids in the early region 1a (e1a) 13s mrna-coding region and in the e1a 12s mrna intron. in203s could not grow in hela and kb cells. virus dna replication was scarcely detected at a low multiplicity of infection, but was detected at a high multiplicity of infection. the transcription of early genes other than e1a was not detected at 13 h after infection, but became detectable after longer incubation. the ...19862935643
the adenovirus type 12 early-region 1b 58,000-mr gene product is required for viral dna synthesis and for initiation of cell transformation.an e1b 58k mutant of adenovirus type 12 (ad12), dl207, was constructed by the deletion of 852 base pairs in the e1b 58k coding region. the mutant could grow efficiently in 293e1 cells but not in hela, kb, or human embryo kidney (hek) cells. viral dna replication of dl207 was not detected in hela and kb cells and was seldom detected in hek cells. analysis of viral dna synthesis in vitro showed that the ad12-dna-protein complex replicated by using the nuclear extract from ad12 wild-type (wt)-infec ...19862936899
mitogenic activity of the adenovirus type 12 e1a gene induced by hormones in rat cells.several lines of rat 3y1 cells in which expression of the adenovirus type 12 e1a gene can be regulated by dexamethasone were established by introduction of recombinant vector dna containing the adenovirus type 12 e1a gene placed downstream of the hormone-inducible promoter of mouse mammary tumor virus. these cell lines (gma cells) produced low basal levels of the e1a transcripts and proteins in normal medium and much higher levels upon addition of dexamethasone to the medium. when dexamethasone ...19862936902
posttranslational modification at the n terminus of the human adenovirus type 12 e1a 235r tumor antigen.the adenovirus e1a transforming region, which encodes immortalization, partial cell transformation, and gene activation functions, expresses two early mrnas, 13s and 12s. multiple-t antigen species with different electrophoretic mobilities are formed from each mrna, presumably by unknown posttranslational modifications. the adenovirus type 12 (ad12) 13s and 12s mrnas encode e1a t antigens of 266 and 235 amino acid residues (266r and 235r), respectively. to study possible posttranslational proces ...19862939260
adenovirus type 12 e1a protein expressed in escherichia coli is functional upon transfer by microinjection or protoplast fusion into mammalian cells.we efficiently expressed, in escherichia coli, and purified the protein product encoded by the human adenovirus type 12 (ad12) 13s mrna. the functional properties of the e1a protein were analyzed by introducing the protein by microinjection or protoplast fusion into living mammalian cells. we showed that the e. coli-expressed e1a protein induces gene expression of the adenovirus type 5 (ad5) e1a deletion mutant ad5dl312. the purified e1a protein rapidly and quantitatively localized to the cell n ...19862942704
requirement of conditioned medium or a high concentration of serum for anchorage-independent growth of adenovirus type 12 e1a-transformed rat cells (hy1).adenovirus type 12 (ad12) ela-transformed rat cells (hy1) grew in methocel medium containing 9% fetal calf serum (fcs), but the frequency of colony formation was very low (the order of 10(-4)). the addition of conditioned medium or a high concentration of serum (20% fcs) to the methocel medium accelerated colony formation, and plating efficiency increased 10- to 100-fold. in contrast, in stationary culture, hy1 cells grew well even in 1%-fcs medium. these results indicate that hy1 cells require ...19872952289
interferon induction by adenovirus type 12: stimulatory function of early region 1a.adenoviruses are generally weak interferon inducers, triggering chicken embryo fibroblast cells by a uv-resistant viral component, probably the capsid or capsid elements, to produce 50 to 100 iu of interferon per ml. adenovirus types 12, 18, and 31, however, can induce by a uv-sensitive mechanism 10 to 20 times more interferon than other types do. by using mutant and recombinant adenoviruses, we demonstrated that early region 1a was responsible for the enhanced interferon production of chicken c ...19872953908
expression of adenovirus type 12 e1b 58-kda protein in escherichia coli and production of antibodies raised against a 58-kda::beta-galactosidase fusion protein.dna fragments coding for the n-terminal 185 amino acids (aa) and for the entire coding region of the adenovirus (ad)12 e1b 58-kda protein have been cloned in a prokaryotic expression vector. the n-terminal region of the 58-kda viral protein (aa 21-205) is expressed as a beta-galactosidase (beta gal) fusion protein encoded by plasmid pb58ngal. escherichia coli strains transformed with this plasmid synthesize a full-length fusion protein of 150-kda and two truncated proteins: a 140-kda protein con ...19872956155
induction of cellular dna synthesis by adenovirus type 12 in a set of temperature-sensitive mutants of rat 3y1 fibroblasts blocked in g1 phase.four temperature-sensitive (ts) mutants of rat 3y1 fibroblasts, which represent separate complementation groups, cease to proliferate predominantly with a 2c dna content, either at 39.8 degrees (temperature arrest), or at 33.8 degrees at a confluent cell density (density arrest). when infected at 39.8 degrees with adenovirus type 12 (ad12), cells of all four ts mutants in both arrest states entered the s phase, thereby suggesting that ad12 overcomes the four independent functional blocks to cell ...19872957848
evidence for the expression of protein ix in some rat cells transformed with adenovirus type 12 early region 1 dna.sera were produced by injection of a particular rat cell line (hlbrk ecoc1), produced by transformation of baby rat kidney cells with adenovirus 12 early region 1 dna, into the syngeneic host. antibodies to a protein of mr 15,200 as determined by sds-page, were detected in the sera from two rats bearing tumours. the 15k protein was identified as the viral structural component polypeptide ix by a number of criteria: (i) the protein was only observed in adenovirus 12-infected cells, (ii) it was pr ...19872958603
activation of the human beta interferon gene by the adenovirus type 12 e1b gene.the transcription of endogenous beta interferon mrna was activated in human embryo kidney (hek) cells infected with adenovirus type 12 (ad12) but was activated only inefficiently or not at all in hek cells infected with ad5 and rc-1 (ad5 dl312 containing the ad12 e1a region). the analysis with ad12 mutants showed that ad12 e1b products, especially the 19k protein, were important for the expression of the endogenous beta interferon gene and ad12 e1a products were not involved in the expression. t ...19882960835
induction of cell cycle progression by adenovirus e1a gene 13s- and 12s-mrna products in quiescent rat cells.rat 3y1 cell lines that express either adenovirus type 12 e1a 13s mrna or 12s mrna in response to dexamethasone treatment were established by introduction of recombinant vector dna containing the e1a 13s- or 12s-mrna cdna placed downstream of the hormone-inducible promoter of mouse mammary tumor virus. these cell lines were growth arrested, and the induction of cell cycle progression was analyzed by flow cytometry after switch on of the cdna by the addition of dexamethasone. the results indicate ...19872960886
selective cytotoxicity of phospholipids and diacylglycerols to rat 3y1 fibroblasts transformed by adenovirus type 12 or its e1a gene.the colony-forming ability of rat 3y1 fibroblasts transformed by adenovirus type 12 (ad12) was drastically reduced when the cells were cultivated for 18 h in medium augmented with 300 micrograms/ml of liposomes composed of either phosphatidylcholine (pc) or phosphatidylinositol. in contrast, those of untransformed 3y1 cells and simian virus 40-transformed and polyomavirus-transformed 3y1 cells were not. the cytotoxicity of pc liposomes was also observed in 3y1 cells transformed by plasmid dna co ...19882961438
host range mutants of adenovirus type 12 e1 defective for lytic infection, transformation, and oncogenicity.the human adenovirus type 12 (h12) e1a region encodes two early proteins of 266 amino acid residues (266r) and 235r whilst the h12 e1b promoter directs the synthesis of two major proteins of 163r and 482r. to determine the functions of e1a and e1b in lytic infection and oncogenic transformation we have isolated and characterized a series of h12 e1 mutants. mutant h12 hr 700 contains a point mutation in exon 1 that alters a single amino acid common to both the 266 and 235r proteins. this mutant s ...19882964753
adenovirus type 12 e1a gene represses accumulation of mhc class i mrnas at the level of transcription.the levels of the class i antigens and mrnas of the major histocompatibility complex (mhc) are greatly diminished in cells transformed by adenovirus type 12 (ad12). although the ad12-transforming gene, e1a, is responsible for reduced class i expression, the site at which e1a blocks accumulation of class i transcripts is not known. in this study, we demonstrate by nuclear run-on assays that in ad12-transformed mouse cells, e1a acts by reducing the rate of transcription of class i genes.19882968712
suppression of block to entry into s phase in cell-cycle mutants of rat 3y1 fibroblasts after transformation by adenovirus type 12.four temperature-sensitive (ts) mutants of rat 3y1 fibroblasts, belonging to separate complementation groups, cease to proliferate in the g1 phase of the cell cycle at a restrictive temperature (39.8 degrees). these ts mutants were transformed at a permissive temperature with adenovirus type 12 (ad12), its e1a gene, or in203s mutant of ad12 which has a mutation in the e1a 13 s mrna unique region. we examined whether the proliferation of the transformed cells would be blocked in the g1 phase, at ...19882968713
adenovirus type 12 e1b 19-kilodalton protein is not required for oncogenic transformation in rats.the adenovirus type 12 mutants in700 and pm700 carry site-specific mutations within the reading frame encoding the e1b 19-kilodalton protein (19k protein) which prevent the production of the intact 19k protein. in cultures of human a549 cells, these mutants grow just as well as the wild-type virus does, but they display a large-plaque (lp), cytocidal (cyt) phenotype. dna in these infected cells is not degraded, but at late times in human kb cells infected by the mutants, the mutants display a dn ...19882969983
adenovirus type 5 and adenovirus type 12 recombinant viruses containing heterologous e1 genes are viable, transform rat cells, but are not tumorigenic in rats.two sets of adenovirus type 5 (ad5)-adenovirus type 12 (ad12) recombinant viruses were constructed and analyzed. in one case the ad12 e1a, e1b, or e1a plus e1b genes were substituted for the corresponding ad5 genes in the ad5 chromosome. the second set contained the ad5 e1a, e1b, or e1a plus e1b genes in place of the cognate ad12 genes in the ad12 chromosome. the hybrid viruses were all viable and expressed the appropriate e1 antigens. they were able to transform secondary rat fibroblasts, but a ...19882970715
adenovirus transcriptional complexes contain eia encoded tumour antigens physically bound to cellular proteins.adenovirus type 12 transcriptional complexes were isolated from cells during the early phase of infection. sedimentation analysis identified a fast sedimenting complex type i and a slow sedimenting complex type ii. both complexes made virus specific rna complementary to all the early genes and both contained viral dna, which in type ii but not in type i had nucleosome like configuration. analysis of the proteins of the complexes with antiserum against ad 12 eia-beta-galactosidase fusion protein ...19882974276
structure of viral dna in a rat cell line transformed by the cloned ecori-c fragment of adenovirus 12.a dna segment carrying viral dna was cloned from a rat cell line transformed by the cloned ecori-c fragment (0 to 16.4 map units) of human adenovirus type 12(ad12), and the viral sequence in the clone was analysed. the cloned segment contained the region from nucleotide positions 118 to 3520 of the ad12 genome in the middle. no unique structure was found at the viral and non-viral dna junctions. when examined the transforming activity, the conserved viral sequence was able to transform rat 3y1 c ...19852997716
adenovirus e1a-mediated regulation of class i mhc expression.expression of class i mhc transplantation antigens has been shown to be reduced in baby rat kidney (brk) cells transformed by highly oncogenic adenovirus type 12 (ad12), as compared with untransformed cells and cells transformed by non-oncogenic ad5. here we show that this reduction of class i expression also occurs in a variety of other primary cell cultures transformed by ad12, and that reduction of class i gene expression occurs for all class i loci. transfection of ad5e1 into class i-negativ ...19863011403
adenovirus type 12 early region 1a proteins repress class i hla expression in transformed human cells.the adenovirus type 12 (ad12) early region 1a (e1a) gene is thought to play a major role in repressing class i major histocompatibility complex expression in transformed rodent cells. however, since transformation by adenovirus requires both e1a and e1b genes, it has not been demonstrated whether the ad12 e1a gene acts alone or synergistically with the e1b gene to accomplish this effect. moreover, it is not known whether the repression of class i antigen synthesis by ad12-transforming gene produ ...19863014539
interaction of immunosuppressive agents and human adenovirus infection in mice.it was examined whether sensitivity of mice to human adenovirus infections is affected by immunosuppressive agents. mice treated with the lymphotropic cytostatic dianhydrodulcitol (dad) or antilymphocytic serum (als) did not become susceptible to human adenovirus type 12 infection, as the virus did not replicate--not even in its component forms--in the animals. on the other hand, the effect of both dad and als on the lymphoid organs of mice was intensified by human adenovirus infection. in tissu ...19863019068
a transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class i genes.the major histocompatibility complex class i antigens play an indispensable role in cell-cell interactions. perturbation of their expression has been shown to have deleterious physiological consequences, including the escape of transformed cells from immune detection. in an attempt to understand how class i genes are regulated, we dissected the ld gene to identify potential control regions. by using a test vector containing the simian virus 40 early promoter placed upstream of the bacterial chlo ...19863025599
differential effects of dna tumor virus nuclear oncogene products on adipocyte differentiation.we have introduced sv40 and polyoma large t antigen- and adenovirus-type 12 e1a genes into mouse 3t3-l1 preadipocyte cells to study the ability of various nuclear oncogene products to modulate cell differentiation. clones expressing e1a products could differentiate into adipocytes faster than the control in spite of the absence of adipogenic inducers, as measured by the appearance of lipid droplets microscopically and by staining accumulated triglycerides with oil red o. however, clones expressi ...19873034667
insertion of adenovirus type 12 dna in the vicinity of an intracisternal a particle genome in syrian hamster tumor cells.in the adenovirus type 12 (ad12)-induced hamster tumor t1111(2) about 10 ad12 genome equivalents were integrated at different sites. one of the integrated copies proved unstable and was lost from the cellular genome or rearranged upon passage of the cell line, h1111(2), established from this tumor. this unstable site of junction between the left terminus of ad12 dna and hamster dna and the preinsertion site from bhk21 hamster cells was cloned, sequenced, and analyzed. the junction site showed se ...19873039166
the primary structure of human adenovirus type 12 protease. 19883043380
expression of hamster mhc class i antigens in transformed cells and tumours induced by human adenoviruses.the steady-state levels of hamster mhc class i mrna and cell surface protein were analysed in cells transformed by either adenovirus type 12 (ad12) or types 2 or 5 (ad2 or ad5). all cell lines were oncogenic in new born and adult hamsters. a great reduction in both class i mrna and protein was observed in ad12 transformed cells compared to cells transformed by ad2 or ad5. analysis of class i mrna in solid tumours induced in hamsters by ad transformed cell lines also showed greatly reduced mrna l ...19883061828
partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the h-2 class i gene h-2ld into a human colon cancer cell line (hct).many human tumors, particularly those of epithelial origin, appear to express greatly reduced levels of major histocompatibility complex class i antigens on their surface. it has been previously reported that the class i gene h-2ld, introduced into adenovirus type 12-transformed mouse cells, induces reversal of oncogenesis in immunocompetent balb/c mice. we have tested the hypothesis that the h-2ld gene, when transfected into hct colon cancer cells, may alter their transformed phenotype. two h-2 ...19883186742
integration of foreign dna into mammalian genome can be associated with hypomethylation at site of insertion.the methylation patterns in the genome of mammalian cells are remarkably stable, although occasional changes are observed. in mammalian cells, the non-methylated dna of human adenovirions (günthert et al., 1976) undergoes de novo methylation after integration into the host hamster genome (sutter et al., 1978). the establishment of these specific patterns of methylation in the integrated adenovirus sequences (sutter and doerfler, 1979, 1980) requires a considerable number of cell divisions after ...19883223064
molecular cloning and characterization of cellular genes whose expression is repressed by the adenovirus e1a gene products and growth factors in quiescent rat cells.several cdna clones of cellular genes, whose expression is repressed by the adenovirus type-12 e1a gene products, were isolated from a rat 3y1 cell cdna library by differential plaque hybridization with labeled cdna probes prepared from 3y1 and the derivative cell line expressing the e1a gene constitutively. the changes in the levels of these gene transcripts during cell-cycle progression from g0 to g1 to s phase were analyzed with 3y1 cells and gma cell lines, derived from 3y1 cells, in which t ...19883266490
cells transformed by adenovirus type 12 but not by type 5 are dependent on insulin or insulin-like growth factor i for their proliferation.we have investigated the responsiveness to growth factors (gfs) of primary baby rat kidney (brk) cells transformed by the e1 region of adenovirus 5 or 12. the in vitro growth of non-oncogenic adenovirus 5-transformed brk cells is largely independent of serum gfs, whereas growth of highly oncogenic adenovirus 12-transformed cells is strictly dependent on gfs present in serum. for the growth of adenovirus 12 e1-transformed brk cells serum can be replaced by insulin or insulin-like growth factor-i ...19883275666
tumorigenicity of adenovirus-transformed cells: collagen interaction and cell surface laminin are controlled by the serotype origin of the e1a and e1b genes.a library of cells transformed with recombinant adenoviruses was used to study tumorigenicity and interaction with extracellular matrix. cells expressing the complete e1 region of highly oncogenic adenovirus type 12 (ad12) are tumorigenic, adhere preferentially to type iv collagen, and express cell surface laminin. weakly tumorigenic cells, which express the e1a oncogene of ad12 and the e1b genes of ad5, also attach preferentially to type iv collagen but do not contain laminin on their surface. ...19883275789
functional expression of a heterologous major histocompatibility complex class i gene in transgenic mice.the regulated expression of major histocompatibility complex class i antigens is essential for assuring proper cellular immune responses. to study h-2 class i gene regulation, we have transferred a foreign class i gene to inbred mice and have previously shown that the heterologous class i gene was expressed in a tissue-dependent manner. in this report, we demonstrate that these mice expressed the transgenic class i molecule on the cell surface without any alteration in the level of endogenous h- ...19873323884
predominant association of adenovirus type 12 dna with human chromosome 1 early in productive infection.in human kb cells productively infected with human adenovirus type 12 (ad12), viral dna can recombine with cellular dna. the functional significance of this covalent linkage is not understood. it is, however, conceivable that very early in the infection cycle integrated viral genes gain an advantage by being transcribed more effectively. in the present study, it has been shown that ad12 dna is associated predominantly with human chromosome number 1 and one chromosome in the cii group. this assoc ...19883341119
isolation and characterization of adenovirus type 12 e1 host-range mutants defective for growth in nontransformed human cells.in order to define the functions of human adenovirus type 12 (ad12) early region 1 (e1) products in lytic infection and oncogenic transformation we have isolated and phenotypically characterized a set of host-range (hr) mutants of this serotype. these mutants grow efficiently upon her3 cells, which contain and express type 12 e1 genes, but are restricted for growth upon a549 carcinoma and hela cells. inter- and intratypic complementation analysis, marker-rescue mapping, and dna sequence analysis ...19883369087
a fragile site in the human u2 small nuclear rna gene cluster is revealed by adenovirus type 12 infection.using in situ hybridization, we found that the u2 small nuclear rna gene cluster mapped very close to and was frequently disrupted by the gaps and breaks induced specifically in the human 17q21-q22 region by highly oncogenic adenovirus type 12 (ad12). restriction mapping revealed no structural alterations in the u2 gene locus as a result of ad12 infection. likewise, no ad12-induced alterations in u2 rna levels were detected. we estimate that the maximum size of the region specifically disrupted ...19883386628
effect of lipid derivatives on invasion in vitro and on surface glycoproteins of three rodent cell types.the antiinvasive activity on mo4 mouse cells of the following lipid derivatives was tested in vitro: an alkyl-lysophospholipid derivative (et-18-och3), a thioether-phospholipid derivative (bm 41.440), an alkyl-linked lipoidal amine (cp-46,665) and a naturally occurring ester-linked phospholipid (2-lpc). in this test, bm 41.440 had the same antiinvasive potency as et-18-och3, whereas cp-46,665 and 2-lpc had no effect on invasion. comparison of the antiinvasive effect of et-18-och3 on three types ...19873444376
trans-activation of a methylated adenovirus promoter by a frog virus 3 protein.the high degree of methylation of the frog virus 3 (fv3) genome suggests that fv3-infected cells are capable of transcribing highly methylated dna. we tested this hypothesis by assaying the transcriptional activity of adenovirus promoters known to be inhibited by methylation. plasmid constructs containing the e1a and e2ae promoters of adenovirus type 12 linked to the gene for chloramphenicol acetyltransferase [(cat) ec 2.3.1.28], when methylated and introduced into eukaryotic cells, promoted cat ...19863463992
expression of major histocompatibility complex class i antigens as a strategy for the potentiation of immune recognition of tumor cells.like many primary tumors, human adenovirus type 12 (ad12)-transformed mouse cells express greatly reduced levels of the major histocompatibility complex (mhc) class i antigens and are highly tumorigenic in immunocompetent hosts. expression of a transfected class i gene by these cells can abrogate their tumorigenicity. both the k and the l class i genes can suppress the malignant phenotype. previous studies showed that interferon can induce class i gene expression in certain ad12-transformed cell ...19863464979
n6-methyldeoxyadenosine residues at specific sites decrease the activity of the e1a promoter of adenovirus type 12 dna.the activity of eukaryotic promoters is highly sensitive to site-specific modifications by dna methylations. we have used the e1a promoter of adenovirus type 12 (ad12) dna to investigate the effects of methylations at different promoter sites on its activity. the chloramphenicol acetyltransferase gene has served as an activity indicator. activity of the e1a promoter is lost or markedly decreased by deoxycytidine methylation of two hpaii (5'-c-c-g-g-3') or seven hhai (5'-g-c-g-c-3') sites upstrea ...19863489102
modulation of the level of expression of cellular genes in adenovirus 12-infected and transformed human cells.the level of expression of thymidine kinase (tk), heat shock protein 70 (hsp70), beta-tubulin and p53 was assessed in human embryo kidney cells (heks) infected with adenovirus type 12 (ad 12) and ad 12 early region 1 (e1) mutants. hsp70, beta-tubulin and p53 levels were unchanged but tk activity was dramatically increased following wild-type infection. the initial activation of tk required the expression of the product of the e1a 13s mrna but sustained expression only occurred with those viruses ...19863525149
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