Mutagenic activity and specificity of N-nitrosomethylaniline and N-nitrosodiphenylamine in Salmonella.
The carcinogenic nitrosamines, N-nitrosomethylaniline (NMA) and N-nitrosodiphenylamine (NDphA), which have been previously reported negative or very weakly mutagenic in the Salmonella/microsome assay, were found to be mutagenic in the hisG428 Salmonella strain, TA104. NMA was moderately potent and NDphA was about 10% as potent. Mutagenesis by both compounds was dependent on the uvrB mutation and enhanced in strains harboring the plasmid, pKM101. The mutational specificities of NMA and NDphA for base-pair substitutions were determined by assaying their activities in several mutants which are reverted by a limited number, or a single type of base-pair substitution mutation, and additionally by subclassification of revertants. NMA induced predominantly AT----CG transversions and NDphA induced AT----TA transversions. The specificity of NMA and NDphA for mutagenesis at AT base pairs and the lack of sensitivity of the previously employed hisG46 strains for these base changes may be the reason for the previous reports on the lack of mutagenic activity of these compounds. This specificity is quite unusual for nitrosamines and is consistent with the hypothesis that NMA and NDphA lead to DNA damage of different nature than that produced by other nitrosamines.
Zielenska
M
M
Department of Biochemistry, New York University Dental Center, NY 10010.
Guttenplan
J B
JB
D001483:Base Sequence; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000378:metabolism / Q000633:toxicity; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D009602:Nitrosamines / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D009602:Nitrosamines; D005557:Formaldehyde; C014102:N-methyl-N-nitrosoaniline; C023649:N-nitrosodiphenylamine