Nitrosated urea pesticide metabolites and other nitrosamides. Activity in clastogenicity and SCE assays, and aberration kinetics in Chinese hamster V79-E cells.

The nitrosoureas 1-methyl-1-nitroso-3-phenylurea, 1-ethyl-1-nitroso-3-phenylurea, 1-methyl-1-nitroso-3-(p-fluorophenyl)urea, 1-methyl-1-nitroso-3-(p-chlorophenyl)urea, and 1-methyl-1-nitroso-3-(p-bromophenyl)urea, as well as their non-nitrosated parent compounds, were checked for induction of chromosomal aberrations and sister-chromatid exchanges in V79-E cells without metabolic activation in vitro. For comparison, methylnitrosourea, ethylnitrosourea and nitrosocarbaryl were included in this study. Whereas the non-nitrosated agents were inactive, the nitroso derivatives were potent clastogens and inducers of SCEs. Clastogenicity parallels SCE induction, but the latter assay is about 10 times more sensitive (based on concentration of substance) than the clastogenicity assay. The dependence of aberration frequency on sampling time, which was studied for 5 nitroso compounds, revealed striking differences. As demonstrated by differential chromatid staining, the lag phase until maximal aberration rates may cover more than 2 cell cycles. Preventive oncological aspects of these nitrosamides and the mechanism of aberration kinetics are discussed.