Effect of CYP3A4 genetic polymorphisms on the genotoxicity of 4,4′-methylene-bis(2-chloroaniline)-exposed workers

Objectives We investigated the relationship between 4,4’-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4). Methods We divided the study population into an exposed group (n=44 with total urine MBOCA ≥20 μg/g creatinine) and a control group (n=47 with total urine MBOCA CYP3A4 alleles were measured by PCR-based restriction fragment length polymorphism (PCR-RFLP). Results The mean MNF (6.11 vs 4.46 MN/1000 cells, p CYP3A4 polymorphism A/A+A/G influenced the difference in the mean MNF (5.97 vs 4.38 MN/1000 cells, p CYP3A4 A/A+A/G genotype. Similarly, the MNC level in the MBOCA-exposed workers was 0.593 MN/1000 cells (p CYP3A4 A/A+A/G genotype. However, the difference in adjusted MNF and MNC between the exposed and control groups was not significant for the CYP3A4 polymorphism with the G/G genotype. Conclusions We recommend that lymphocytes MNF and MNC are good indicators to evaluate MBOCA genotoxicity. Individuals with the CYP3A4 polymorphism A/A and A/G genotypes appear to be more susceptible to MBOCA genotoxicity.