Relationship of simian virus 40 tumor antigens to virus-induced mutagenesis.

Zannis-Hadjopoulos, M; Martin, R G

doi:10.1128/mcb.3.3.421

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…Investigators have reported no mutagenic effect of SV40 in some experiments and 12-fold or greater increases in the frequency of mutants in other experiments. Conflicting results have been obtained regarding the role of T antigen in SV40-mediated mutagenesis (13,(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the mutagenic effects of SV40 in mouse, hamster, and mouse-human hybrid cells

Giles

Boyce

Brockman

1991

Somat Cell Mol Genet

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We have examined the ability of SV40 to induce changes in drug or temperature resistance in mouse, hamster, and mouse-human hybrid cells. SV40 induced a substantial increase of cells resistant to 5-bromodeoxyuridine + trifluorothymidine in Balb/c 3T3 cells and induced an increase of hybrid cells resistant to 6-thioguanine. SV40 was found to be nonmutagenic or weakly mutagenic in other test systems. The 3T3 cells were T-antigen positive, exhibited a marked reduction in TK activity, were heterogeneous for [3H]BrdU incorporation by autoradiography, and exhibited instability of the drug-resistance phenotype, suggesting that SV40 may be inducing resistance by an epigenetic process. SV40-induced 6-thioguanine resistance in the hybrids appears to occur predominantly by chromosome loss.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the mutagenic effects of SV40 in mouse, hamster, and mouse-human hybrid cells

Giles

Boyce

Brockman

1991

Somat Cell Mol Genet

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“…In a previous report, we made use of the XC cell line, which is not permissive for HSV-2, to demonstrate that intact viral particles could increase the frequency of HPRT-mutants by factors ranging from 2.4 to 10.3 (38). Other DNA viruses such as simian virus 40 and adenovirus type 2 can cause mutations at several loci in nonpermissive infections (14,27,28,50,52,60). However, the nature of the virally induced mutations has not been systematically studied at the molecular level, and the mutational mechanism of these viruses is not known.…”

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confidence: 99%

Herpes simplex virus type 2 mutagenesis: characterization of mutants induced at the hprt locus of nonpermissive XC cells.

Pilon¹,

Langelier²,

Royal³

1986

Mol. Cell. Biol.

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. 66:259-265, 1985). A series of 17 independent mutants were isolated after viral infection together with 12 spontaneous noninfected mutants to characterize the nature of the mutations induced by the virus at the molecular level. The DNA of the mutants isolated after viral infection was probed with cloned HSV-2 fragments representing the entire genome. In these mutants, no authentic HSV-2 hybridization could be detected. This was indicative of a mechanism of mutagenesis which did not require the permanent integration of viral sequences in the host genome. The structure of the hprt gene was determined by the method of Southern (J. Mol. Biol. 98:503-517, 1975), and the level of hprt mRNA was analyzed by Northern blots. Except for the identification of one deletion mutant in each of the two groups, the HPRT-clones showed no evidence of alteration in their hprt gene. A total of 7 of 12 spontaneous mutants and 11 of 15 mutants isolated from the infected population transcribed an hprt mRNA of the same size and abundance as did the wild-type cells. Thus, the majority of the mutants seemed to have a point mutation in their hprt structural gene.Interestingly, the proportion of the different types of mutations was similar in the two groups of mutants. This analysis revealed that HSV-2 infection did not increase the frequency of rearrangements but rather that it probably induced a general increase of the level of mutations in the cells. This type of response is thought to be compatible with the biology of the virus, and the possible mechanisms by which HSV-2 induces somatic mutations in mammalian cells are discussed.Defined regions of the herpes simplex virus type 2 (HSV-2) genome can transform rodent cells in vitro (12,20), but the existence of a viral oncogene responsible for the maintenance of the transformed state has been questioned because of the lack of evidence that a specific viral sequence was retained in these cells (13). In addition, transformation by HSV is less efficient (13,20,21) than what is generally observed with viral oncogenes (3, 29). These considerations suggested that the role of the virus was transient and led to the hypothesis that HSV acts as a mutagen (13,17,42,61). The first evidence that HSV could cause mutations came from observations that infection often results in fragmentation and pulverization of cellular chromosomes (4,16,45,57). It was subsequently shown by Schlehofer and zur Hausen (41) that infection of human permissive rhabdomyosarcoma cells by inactivated HSV-1 could result in an increased mutation frequency at the hypoxanthine phosphoribosyltransferase (hprt) locus. In a previous report, we made use of the XC cell line, which is not permissive for HSV-2, to demonstrate that intact viral particles could increase the frequency of HPRT-mutants by factors ranging from 2.4 to 10.3 (38). Other DNA viruses such as simian virus 40 and adenovirus type 2 can cause mutations at several loci in nonpermissive infections (14,27,28,50,52,60). However, the nature of the virally induced mutations h...

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Frequent spontaneous sister chromatid exchange in hepatocytes of transgenic mice harboring the SV40-T antigen gene

Liu

Nomura

et al. 1992

J Cancer Res Clin Oncol

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In order to shed light on the causal mechanisms of hepatocarcinogenesis in the transgenic mouse into which the albumin-promotor-regulated SV40-T antigen gene has been introduced (T+ mouse), and especially on the frequent chromosomal aberrations seen in cultured hepatocytes and hepatocellular neoplasms derived from such animals, the frequency of sister chromatid exchange (SCE) and karyotype abnormalities were investigated in a hepatocyte primary culture system. Cells were obtained through collagenase perfusion from T+ mice at 16-18 days of age, when no morphological changes are apparent, and from nontransgenic littermates, and cultured in the presence of bromodeoxyuridine. SCE was seen in transgenic hepatocytes twice as frequently as in their normal counterparts. No karyotype abnormalities in terms of numerical change or gross aberration were detected at this phase. The results thus suggest mutagenic properties for the T antigen, which may play an important role in hepatocarcinogenesis in this transgenic mouse.

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Relationship of simian virus 40 tumor antigens to virus-induced mutagenesis.

Cited by 4 publications

References 14 publications

Evaluation of the mutagenic effects of SV40 in mouse, hamster, and mouse-human hybrid cells

Evaluation of the mutagenic effects of SV40 in mouse, hamster, and mouse-human hybrid cells

Herpes simplex virus type 2 mutagenesis: characterization of mutants induced at the hprt locus of nonpermissive XC cells.

Frequent spontaneous sister chromatid exchange in hepatocytes of transgenic mice harboring the SV40-T antigen gene

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