Mutagenicity of 4-aminobiphenyl and 4-acetylaminobiphenyl in Salmonella typhimurium strains expressing different levels of N-acetyltransferase

4-Aminobiphenyl (4-ABp), an aromatic amine present in tobacco smoke, is an animal and human carcinogen. CABP can undergo several biotransformation reactions to yield DNA-binding species. The role of acetylation in the biotransformation of 4-ABP to reactive intermediates was investigated by determining mutagenicity in Salmonella typhimurium strains expressing various levels of acetyltransferases (NAT/OAT). Strain YG1029, which has multiple copies of the NAT/OAT gene, was the most sensitive to CABP. With rat S9 activation, CABP (5 mu g/plate) induced 789 +/- 98 revertants/plate. At that concentration, an average of 200 revertants/plate was seen in both TA100, which has a single copy of the NAT/OAT gene, and in TA100/1,8DNP(6), which is NAT/OAT deficient. This pattern was also present when the bacteria were exposed to the acetylated derivative, 4-acetylaminobiphenyl (4-AABP). At 10 mu g/plate, 4-AABP induced 855 +/- 47 revertants/plate in YG1029 while 169 +/- 39 and 149 +/- 28 revertants/plate were observed in strains TA100 and TA100/1,8DNP(6), respectively. The mutagenic profiles of CABP and 4-AABP observed with the mouse S9 activating system were similar to that seen with the rat. These data establish a correlation between increased bacterial NAT/OAT activity and increased mutagenicity of CABP. Results with both 4-ABP and 4-AABP support acetylation of the oxygen to be a key step in activation. (C) 1999 Academic Press.