Genetics of somatic mammalian cells. IX. Quantitation of mutagenesis by physical and chemical agents

TLDR

The mutation system in Chinese hamster cells has been expanded to generate additional auxotrophic mutants. The study presents methods for routine in‑vitro testing of drugs, food additives, and environmental pollutants for mutagenic activity. The authors measured single‑cell survival curves and chromatid breakage/rearrangement efficiencies for each mutagen, including N‑nitrosomethylurea. An improved quantitation method revealed that various agents induce single‑gene mutations, linking cell killing, chromosomal aberrations, and carcinogenesis.

Abstract

Abstract The system previously described for inducing single gene mutations in Chinese hamster cells has been extended to produce additional auxotrophic mutants. An improved method for quantitating the efficiency of single gene mutation to specific auxotrophies has been developed. Mutagenesis in the forward direction has been measured after treatment of these cells with ethyl methanesulfonate, N‐methyl‐N 1 ‐nitro‐N‐nitrosoguanidine, hydroxylamine, an acridine mustard (ICR‐191), caffeine and ultraviolet‐ and X‐irradiation. For each agent, the single cell survival curve and the efficiency of chromatid breakage and rearrangement were measured. Similar measurements were also carried out with a water‐soluble carcinogen N‐nitrosomethylurea, which was shown to be effective in producing auxotrophic, somatic mutations. These results offer promise of illuminating the relationships between cell killing, chromosomal aberration, single gene mutations and carcinogenesis produced by various agents. The methods described can be used in routine testing of drugs, food additives, and environmental pollutants for mutagenic action in mammalian cells in vitro .