Effect of N-glucuronidation on urinary bladder genotoxicity of 4-aminobiphenyl in male and female mice

Urinary bladder cancer is the fourth most commonly diagnosed malignancy in men and the tenth most commonly diagnosed malignancy in women in the US. Arylamines have long been associated with bladder cancer and several studies documented that men exposed to arylamines (cigarette smokers, hairdressers, and workers of dye and textile industries) have several times increased risk compared to women. N-glucuronidation is an important phase II conjugation reaction that delivers the active metabolites of arylamines from the liver to the urinary bladder. In the current study, we found that male mice are more active in 4-ABP N-glucuronidation than female mice and this difference was statistically significant. In the in vivo experiments, male and female mice (strain C57BL/6) were treated with 4-ABP after modulating their 4-ABP N-glucuronidation using the plant steroid, hecogenin. The distribution of 4-ABP adducts in liver and bladder was then determined. In animals treated with 4-ABP only, males had statistically significant higher levels of DNA adducts in the bladder (p-value 0.0004) while females had statistically significant higher levels in the liver (p-value