Amino acid conjugation of N-hydroxy-4-aminoazobenzene dyes: a possible activation process of carcinogenic 4-aminoazobenzene dyes to the ultimate mutagenic or carcinogenic metabolites.

The activation process of N-hydroxy-4-aminoazobenzene (N-OH-AAB) dyes, proximate mutagenic or carcinogenic metabolites of AAB dyes, to the ultimate mutagenic or carcinogenic metabolites was studied by the use of an amino acid conjugation (aminoacylation) system catalyzed by yeast seryl-tRNA synthetase and [3H]ATP. A potent mutagen, N-hydroxy-3-methoxy-AAB (N-OH-3-MeO-AAB), as well as a non-mutagen, N-OH-2-MeO-AAB, were equally susceptible to N-O-serine conjugation. A weak mutagen, N-OH-AAB, and a moderate mutagen, N-OH-2,5-diMeO-AAB, were also susceptible to the aminoacylation, but to a lesser extent than the 2- or 3-methoxyl homologs. In contrast, N-hydroxy-N-methyl-4-aminoazobenzene and a moderate mutagen, N-OH-4'-MeO-AAB, were not susceptible to the aminoacylation. The ability of these N-OH-AAB dyes to bind with nucleic acid after serine conjugation was proportional to the susceptibility of the dyes to serine conjugation. Serine conjugates of N-OH-AAB dyes reacted with poly G, but not with poly A, poly C or poly U, suggesting that the azo dyes selectively bind with guanine base of nucleic acids. The susceptibility of N-OH-AAB dyes to aminoacylation was compared with the carcinogenic, mutagenic and unscheduled DNA synthesis-inducing activities of these and the mother AAB dyes.