Strain and Sex Differences in the Hepatotoxicity of 4-Aminobiphenyl in the Mouse

• Main Author: Emami, Arian
• Other Authors: Grant, Denis M.
• Language: en_ca
• Published: 2010
• Subjects: Aromatic amine; Cytotoxicity; 4-Aminobiphenyl; Tumorigenesis; 4-ABP; Mouse strain; Hepatotoxicity; Gender disparity; Strain disparity; Chemical carcinogenesis; Hepatocellular carcinoma; HCC; Carcinogenesis; ABP
• Online Access: http://hdl.handle.net/1807/25567

Recent studies from our laboratory on the aromatic amine carcinogen, 4-aminobiphenyl (ABP) have shown a significantly lower prevalence of ABP-induced liver tumors in male mice lacking the N-acetyltransferases, and a dramatically lower prevalence in females than in males, but no association of tumor prevalence with strain or sex differences in levels of acute ABP-induced DNA damage. This thesis aimed to investigate the possible involvement of acute cytotoxic effects of ABP in the development of a tumor-promoting inflammatory environment. We found that wild-type male mice showed higher acute hepatotoxicity to ABP, as well as, a possible trend towards higher serum levels of the pro-inflammatory cytokine interleukin 6. This correspondence between acute ABP cytotoxicity and inflammatory response with ultimate tumor growth is consistent with a model whereby ABP not only initiates cells by damaging DNA but also promotes tumor growth in a gender-selective fashion that may be governed by gonadal hormone influences.