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

Authors: Dang, L N; McQueen, C A

Published In Toxicol Appl Pharmacol, (1999 Sep 1)

Abstract: 4-Aminobiphenyl (4-ABP), an aromatic amine present in tobacco smoke, is an animal and human carcinogen. 4-ABP 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 4-ABP. With rat S9 activation, 4-ABP (5 micrograms/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 TA100/1,8DNP6, 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 micrograms/plate, 4-AABP induced 855 +/- 47 revertants/plate in YG1029 while 169 +/- 39 and 149 +/- 28 revertants/plate were observed in strains TA100 and TA100/1,8DNP6, respectively. The mutagenic profiles of 4-ABP 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 4-ABP. Results with both 4-ABP and 4-AABP support acetylation of the oxygen to be a key step in activation.

PubMed ID: 10495770

MeSH Terms: No MeSH terms associated with this publication