Unscheduled DNA synthesis induced by 4-aminoazobenzene, N-hydroxy-4-aminoazobenzene, and their derivatives in primary cultures of rat and mouse hepatocytes.

The ability of carcinogenic and non-carcinogenic aminoazo dyes to induce unscheduled DNA synthesis (UDS) in primary cultures of hepatocytes of 3 strains of rats and 2 strains of mice was examined by means of microautoradiography. Azo dyes tested were 4-aminoazobenzene (AAB) and 4 of its ring methoxyl (MeO) derivatives, their N-hydroxy (N-OH) derivatives, N-methyl-4-aminoazobenzene (MAB) and its N-bezoyloxy derivative, and N,N-dimethyl-4-aminoazobenzene (DAB). All carcinogenic aminoazo dyes (AAB, 3-MeO-AAB, 4'-MeO-AAB, MAB and DAB), but not the non-carcinogenic dyes (2-MeO-AAB and 2,5-diMeO-AAB), induced UDS in rat hepatocytes as well as mouse hepatocytes. N-Hydroxy derivatives of AAB and its 3- and 4'-MeO derivatives elicited higher levels of UDS than did the corresponding mother aminoazo dyes. N-OH-2-MeO-AAB was as inactive with rat hepatocytes as the mother dye. N-OH-2,5-diMeO-AAB, however, elicited a definite level of UDS, in contrast to the mother 2,5-diMeO-AAB. N-Benzoyloxy-MAB, a prototype compound of the ultimate carcinogenic metabolite of MAB, was as active as the mother MAB. N,-OH-3-MeO-AAB induced UDS more rapidly than did 3-MeO-AAB. The UDS elicited by 3-MeO-AAB was found to end within a few hours after releasing the hepatocytes from the azo dye.