Mutagenic selectivity for the RNA-forming genes in relation to the carcinogenicity of alkylating agents and polycyclic aromatics.

Selective mutagenicity was studied in Drosophila for 2 groups of carcinogenic chemical series with divergent intrinsic reactivities towards cellular macromolecules: (a) the reactive alkylating and nitroso compounds; and (b) the nonreactive polycyclic hydrocarbons, aromatic amines, and azo dyes. Genetic activity with each compound was examined with respect to the specific effects on the RNA-forming genes (yielding bobbed and Minute mutations) and the nonspecific overall genetic damage as indicated by the X chromosome recessive lethals and visibles. General mutagenic activity on the X chromosome was invariably high with compounds that can effect biological alkylation, but it was extremely low, or nonexistent, with the nonreactive series. The levels of mutagenic selectivity for the rRNA loci with the different compounds were measured as the ratios of their yields of bobbed mutants relative to the overall X mutations induced in the same sample of treated gametes. These ratios varied significantly for compounds within each of the reactive and nonreactive chemical groups, but the differences were much more marked between them, being dramatically higher for the polycyclic aromatics. Carcinogens among all chemical series proved highly active on the RNA-forming loci, particularly the rRNA genes. This was largely or exclusively due to target selectivity for the strongly carcinogenic hydrocarbons and aromatic amines but was partly a function of the general high mutagenic activity for the oncologically active representatives among the alkylating and nitroso compounds.