Spontaneous, chemical and viral mutagenesis in temperature-sensitive glutamine-requiring chinese hamster cells

Varshaver, Nina B.; Marshak, Marina I.; Luss, Eugeny V.; Gorbunova, L. V.; Shapiro, N.I.

doi:10.1016/0027-5107(77)90010-0

Cited by 25 publications

(12 citation statements)

References 20 publications

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“…1 107 U/mg protein). IFN preparations were titered by the semimicro titration procedure of Havell and Vilcek'10' on either human diploid fibroblast cell line 76-109 (popula¬ tion doubling level 35) or Muntjac cells, with no significant difference seen between with either cell line. Vesicular stomatis virus (VSV), donated by Dr. L. Pfeffer (Rockefeller University), was used in these assays.…”

Section: Interferon Treatmentmentioning

confidence: 99%

Chromosomal Aberrations in Muntjac Cells Resulting From Exposure to Interferon

Jasny¹,

Tamm²

1985

Journal of Interferon Research

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Cells of the Indian deer (Muntiacus muntjac) are sensitive to the antiviral and antiproliferative action of human beta-interferon (beta-IFN). Because of their low diploid chromosome number and readily identifiable chromosomes, they provide a convenient model system in which to test for the ability of IFN treatment to result in chromosome abnormalities. Increases in the frequencies of chromosome gaps and breaks have been observed after 72 h of treatment with IFN at a concentration of 100 U/ml. At IFN concentrations of 10-100 U/ml, there is a higher proportion of aberrations in the X chromosome than would be expected in a random distribution. At 1,000-1,700 U/ml IFN, there is an increase in the proportion of cells with multiple abnormalities over that observed at 0-100 U/ml IFN, and the distribution of aberrations appears to be random.

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Section: Interferon Treatmentmentioning

confidence: 99%

Chromosomal Aberrations in Muntjac Cells Resulting From Exposure to Interferon

Jasny¹,

Tamm²

1985

Journal of Interferon Research

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“…DNA viruses can induce mutations when infecting non-permissive cells (Theile et al, 1979;Marengo et al, 1981). For instance, simian virus 40 infection of non-permissive cells leads to an increase in mutation frequencies at different loci including those encoding hypoxanthine-guanine phosphoribosyl transferase (HGPRT) (Marshak et al, 1975), thymidine kinase and dihydrofolate reductase (Theile et al, 1976(Theile et al, , 1979 and reversion of glutamine (Varshaver et al, 1977) and methionine auxotrophy (Hoffman et al, 1978). Finally, HSV is able to cause chromosomal breaks and rearrangements in infected cells (Stich et al, 1964;Waubke et al, 1968).…”

Section: Introductionmentioning

confidence: 99%

Increased Mutation Frequency after Herpes Simplex Virus Type 2 Infection in Non-permissive XC cells

Pilon¹,

Royal²,

Langelier³

1985

Journal of General Virology

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SUMMARYThe effect of herpes simplex virus type 2 (HSV-2) infection on the frequency of mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus was studied in the non-permissive XC cell line. When the cells were infected with 20 to 800 p.f.u./cell, there was initially a lag in cell growth and cell death, but after 4 days there was no difference in growth rate between infected and control cultures. However, the mutation frequency, as determined by the number of 6-thioguanine-resistant colonies, was increased in infected cultures by factors ranging from 2-5 to 10.3. This effect was found to be dependent on the multiplicity of infection. The maximum effect was obtained between 20 and 100 p.f.u./cell while further increase in the amount of virus resulted in a drop in the yield of mutants. The optimum multiplicity of infection was a reproducible characteristic but was variable between viral stocks. When a number of mutant clones were examined they were found to have HGPRT activities ranging from undetectable to 6"9~ of wildqype, indicating that the mutations were in the HGPRT gene. These results show that, in a non-productive infection, HSV-2 particles can increase the mutation frequency. The possible mechanisms by which this effect is brought about in the host genome are discussed.

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“…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.Several reports suggest that simian virus 40 mostly induces point mutations (47,51,56). In these studies, the nature of the mutations was determined by analyzing the * Corresponding author.…”

mentioning

confidence: 99%

“…Several reports suggest that simian virus 40 mostly induces point mutations (47,51,56). In these studies, the nature of the mutations was determined by analyzing the * Corresponding author.…”

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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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Spontaneous, chemical and viral mutagenesis in temperature-sensitive glutamine-requiring chinese hamster cells

Cited by 25 publications

References 20 publications

Chromosomal Aberrations in Muntjac Cells Resulting From Exposure to Interferon

Chromosomal Aberrations in Muntjac Cells Resulting From Exposure to Interferon

Increased Mutation Frequency after Herpes Simplex Virus Type 2 Infection in Non-permissive XC cells

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

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