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Quantitative analysis of mammalian cell mutagenesis

Conference ·
OSTI ID:6353002
The CHO/HGPRT assay was used to quantify cytotoxicity and mutation at the hgprt locus induced by various chemicals. We found that this assay is useful to study structure-mutagenicity relationships as exemplified by a study with 10 direct-acting alkylating chemicals. Within each structurally related group (nitrosamidines, nitrosamides, alkyl alkanesulfonates and alkylsulfates), chemical reactivity (s value) decreases with the size of the alkyl group with the methyl agent being more mutagenic and cytotoxic than the corresponding ethylating chemical on an equimolar basis but not equitoxic level. Both the toxic nature of and the DNA lesions induced by a chemical affect the determination of mutagen potency. When the CHO/HGPRT assay is coupled with a metabolic biotransformation system (S9-mix) the mutagenic activity of promutagens can be quantified. These studies demonstrate that quantitative mutagenesis is affected in a complex fashion by such factors as concentration, toxicity, quality and quantity of DNA lesions, and the effect of different mutagen activation and inactivation systems. 22 references, 1 table.
Research Organization:
Oak Ridge National Lab., TN (USA); Kentucky Univ., Lexington (USA). Graduate Center for Toxicology; Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.). Inst. fuer Biochemie
DOE Contract Number:
AC05-84OR21400
OSTI ID:
6353002
Report Number(s):
CONF-8309279-1; ON: DE85001541
Country of Publication:
United States
Language:
English