Mutagenicity of nitrosated alpha-amino acid derivatives N-acetyl-N'-nitrosotryptophan and its methyl ester in bacteria.
DL-N-acetyl-N'-nitrosotryptophan (I) and its methyl ester (II), readily formed under mild conditions by the reaction of nitrite with N-acetyltryptophan or its methyl ester, are model compounds for the study of the nitrosation of alpha-amino acid side chains, considered relevant to possible role of nitrosation of peptides and proteins in the aetiology of gastrointestinal cancer. Both compounds were assayed for mutagenicity in a series of Escherichia coli WP2 strains (trp- leads to trp+) and in several strains of Salmonella typhimurium (his- leads to his+), in the presence and absence of a post-mitochondrial supernatant (S9) from livers of rats treated with Aroclor 1254. Compound I was mutagenic to the following E. coli strains: WP2; WP2uvrA; WP2pKM101; WP2-98 and TA 100. Compound II was consistently less mutagenic than compound I to the E. coli strains, inactive in S. typhimurium TA 98 and TA 100, but more active than I in TA 1535. Neither compound was detectably mutagenic to E. coli WP2 lexA. Addition of S9 did not enhance the mutagenicity of either compound, and in some cases reduced the mutagenic to any of the E. coli strains tested, and nitrite alone (at pH 7.1) was very feebly mutagenic at doses where molar equivalents of compounds I were markedly active. The rate of decay of compound I in pH 5.9 was closely paralleled by decay of its mutagenicity. These data and the pattern of cytotoxicity and mutagenicity in several DNA-repair mutants of E. coli suggest that both compounds react with DNA to form excisable DNA-adducts which cause mutation by error-prone repair.
D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006868:Hydrolysis; D009153:Mutagens; D009602:Nitrosamines / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014364:Tryptophan / Q000378:metabolism
D009153:Mutagens; D009602:Nitrosamines; C031840:N-acetyl-N'-nitrosotryptophan; C031831:N-acetyl-N'-nitrosotryptophan methyl ester; D014364:Tryptophan