Date of Award
School of Arts and Sciences
Dr. David W. Hein
Polymorphic expression of the arylamine N-acetyl transferases (NAT) in humans has been correlated with genetic predisposition to bladder cancer, but the molecular basis for the differential susceptibility is not fully understood. The inbred Syrian hamsters used In this study, with clearly defined acetylator genotypes, expressed acetylator genotype dependent NAT activity in crude and partially purified bladder cytosol, with apparent Vmax about 6- to 46- fold higher in rapid acetylators, concordant with genotypic expression of hepatic NAT activity. Parallel in vivo and in vitro genotoxicity assays detected higher levels of hepatic arylamine-DNA adducts (1.5- to 2.3-fold) and mutagenic acti-vation (2-fold) in slow than in rapid acetylator hamsters. The results suggest a critical modulating effect of the N-acetylation polymorphism on arylamine-induced genotoxicity and may be a critical factor in determining susceptibility to arylamine-induced bladder cancer.
Yerokun, Tokunbo, "The role of Acetylator Genotype in the expression of Urothelial N-Acetyltransferases and Genotoxic activation of Arylamines in the inbred Hamster system." (1989). ETD Collection for AUC Robert W. Woodruff Library. 394.