This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fahmy, O. G. Articles by Fahmy, M. J. Search for Related Content PubMed PubMed Citation Articles by Fahmy, O. G. Articles by Fahmy, M. J.

Genetic Properties of N--Acetoxymethyl-N-methylnitrosamine in Relation to the Metabolic Activation of N,N-Dimethylnitrosamine¹

Department of Genetics, Institute of Cancer Research, Chester Beatty Research Institute, Royal Cancer Hospital, Fulham Road, London SW3 6JB, England

A genetic study was undertaken in Drosophila with N--acetoxymethyl-N-methylnitrosamine, a precursor of the -hydroxymethyl derivative of N,N-dimethylnitrosamine, to assess the role of -carbon oxidation in toxicological activation. Genetic activity was measured for the whole testicular tissue with respect to the general response of the X chromosome (recessive lethals and visibles), as well as certain specific genic sites, including representatives of the RNA genes.

The biological activity of the acetoxy compound proved to be considerably higher than that of the parent amine with respect to both cytotoxicity and mutagenicity. At low and equitoxic molarities of the 2 agents (0.1 to 1.0 and 1.0 to 10.0 mM, respectively), dose dependence for all the investigated genetic functions followed identical patterns, which were best described by quadratic dose curves. However, the regression coefficients for the acetoxy derivative were at least 1 order of magnitude higher than the corresponding values for the amine, indicating a consistent level of mutagenic activation as a result of the -acetoxymethyl substitution.

At mutagenically equivalent doses, the 2 compounds gave statistically comparable frequencies of mosaicism among corresponding mutational classes and equal ribosomal DNA selectivity indices, indicating identical molecular mechanisms of mutagenesis.

The higher mutagenicity of N--acetoxymethyl-N-methylnitrosamine compared to N,N-dimethylnitrosamine was paralleled by its higher carcinogenicity which would suggest that the same effective metabolites might be involved in both processes.

¹ This work was supported by grants to the Institute of Cancer Research (Chester Beatty Research Institute, Royal Cancer Hospital) from the Medical Research Council and the Cancer Research Campaign.

Received 6/16/75. Accepted 9/ 8/75.