Inter-Individual Variation in the Metabolic Activation of Heterocyclic Amines and Susceptibility to Prostate Cancer
Abstract
The etiology of human prostate cancer is not well understood. Epidemiological studies suggest that exposure to carcinogenic heterocyclic amines (RCA) such as PhIP formed in high-temperature cooked meatfish is an important risk factor. The Phase 1 metabolism of PhIP in human is mainly catalyzed by CYP enzymes, which leads to the formation of 2-hydroxamino-PhIP (N-hydroxy PhIP), the carcinogenic, metabolite, and 4'-hydroxy PhIP (4'-hydroxy PhIP), the non-carcinogenic metabolite. In the present study, we established a highly sensitive LC/MS method and used it to determine the capability of human prostate tissues (n=31) in metabolizing PhIP and other carcinogenic HCA. Our results indicate that there is no significant N- hydroxylation of PhIP, IQ, MeIQ and MeIQx in human prostate microsomes. We also characterized the functional significance of 15 polymorphic variants of CYP1B1 which is a major human enzyme for PhIP metabolic activation in extrahepatic tissues. Results of our study' provide important information on the understanding of inter-individual, susceptibility to prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA470103
Entities
People
- Jun-yan Hong
Organizations
- University of Medicine and Dentistry of New Jersey