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Postreplication repair and the susceptibility of Chinese hamster cells to cytotoxic and mutagenic effects of alkylating agents

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
;
A cell variant (VR-43 resistant to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N'-nitro-N-nitrosourea was isolated from Chinese hamster V79 cells for use in studies of the relationship among cell survival, mutagenesis, and DNA repair by alkylating agents. After treatment with N-methyl-N'-nitro-N-nitrosoguanidine, the VR-43 cells exhibited mutation frequencies that were lower, on a dose basis, than those of the wild-type V79 cells. However, when analyzed at equicytotoxic doses, the VR-43 cells were more mutable than the V79 cells. No difference in cell survival or mutagenicity could be observed after treatment with other mutagens such as N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, or x-rays. After treatment with N-methyl-N'nitro-N-nitrosoguanidine, the VR-43 cells exhibited an enhanced postreplication repair relative to the V79 cells. Based on these results we propose that, after treatment of these and presumably other mammalian cells with some methylating mutagens, postreplication repair can cope with DNA lesions responsible for cytotoxicity and, to a lesser degree, with lesions responsible for mutagenicity.
Research Organization:
Oak Ridge National Lab., TN
DOE Contract Number:
W-7405-ENG-26
OSTI ID:
6756987
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 77:10; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
AMINES
ANIMAL CELLS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBOHYDRATES
CARBONIC ACID DERIVATIVES
CARDIOTONICS
COMPARATIVE EVALUATIONS
DNA
DRUGS
ELECTROMAGNETIC RADIATION
GLYCOSIDES
GUANIDINES
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IONIZING RADIATIONS
MUTAGENESIS
NITROSO COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OUABAIN
PURINES
RADIATIONS
RECOVERY
REPAIR
STEROIDS
STROPHANTIN
SURVIVAL CURVES
UREA
X RADIATION