Date of Award

7-1-1989

Degree Type

Dissertation

School

School of Arts and Sciences

Degree Name

Ph.D.

Department

Biology

First Advisor

Dr. David W. Hein

Abstract

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.

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Biology Commons

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