Rapid and intermediate N-acetylators are less susceptible to oxidative damage among 4,4'-methylenebis(2-chloroaniline) (MBOCA)-exposed workers

摘要

Objectives: In this study, we explored the association between a marker of oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG), and genetic polymorphism of the carcinogen-metabolizing enzyme N-acetyltransferase 2 (NAT2) among 4,4'-methylenebis(2-chloroaniline) (MBOCA)-exposed workers. Methods: The study population was recruited from four MBOCA-producing factories, and included 57 MBOCA-exposed workers and 101 unexposed control workers. Personal characteristics were collected by questionnaire. Plasma 8-OHdG levels were measured by LC/MS/MS. NAT2 alleles were measured by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results: NAT2 polymorphism influenced the plasma 8-OHdG levels of MBOCA-exposed workers, but not of non-exposed workers. No difference between exposed and control groups was found for the crude 8-OHdG levels among rapid, intermediate, and slow acetylators. After adjusting for gender, age, smoking, and alcohol consumption habit, the 8-OHdG concentration in the MBOCA-exposed workers was 0.18pg/ml (95% CI -1.80 to -0.12) lower than the control group among rapid and intermediate acetylators. However, the difference between exposed and control groups was not significant for slow acetylators. Conclusion: Gene-environment interactions could play a role in the carcinogenesis of occupational MBOCA exposure. We suggest that the impact of the NAT2 acetylator status is low, if at all, on the generation of the oxidative stress marker 8-OHdG in the investigated exposed group.