Differential mutagenicity of the amine and amide derivatives of nitroso compounds in Drosophila melanogaster

Abstract

The mutagenicity of N-diethyl- N-nitrosamine (DEN) was compared with that of N-ethyl- N-nitrosourethane (ENU) as regards: non-disjunction, XO males, translocations, induced crossing-over in the male, sex-linked recessive lethals and the elimination of y + and B from a marked Y-chromosome. All phenomena were followed in daily sperm samples from injected males (30 ± 5 h old) bred at unity mating pressure (equal male to female ratio). The various genetic effects were simultaneously determined on the same sample of treated cells or testes, so as to enable the assessment of the relative yield of different mutations. Activity as regards non-disjunction was low with both compounds, but there were occasional indications of some rise in its frequency within the 11th–14th days, thus marking the period of utilization of the meiotic spermatocytes. Induced crossing-over was first sampled on the 10th or 11th day; small clusters of identical or complementary recombinants occurred on the 12th–14th days and the larger ones from the 15th day. Accordingly, the post-meiotic sector of the germ line (sperm and spermatids) was sampled during the first 9 days and the pre-meiotic (spermatocytes and spermatogonia) from the 10th day onwards, with the gonia mainly starting on the 15th day. The yield of the sex-linked recessive lethals was roughly the same for the pre- a and post-meiotic stages with DEN, but was considerably higher for the more mature stages with ENU. There was virtually no activity with either compound as regards the induction of chromosome breaks: both did not induce XO males, and were inactive for translocations. Deletion of the Y-markers occurred with both compounds, but was almost restricted to the pre-meiotic stages with DEN, while extending to the post-meiotic sector with ENU. The induction of deletions relative to lethals with both compounds was higher for the pre- than for the post-meiotic sector, but the degree of this differential response was more marked with DEN. The differences in the mutagenicity of the tested compounds were discussed in relation to their biochemical properties and carcinogenic effects.