MGMT hypomethylation is associated with DNA damage in workers exposed to low-dose benzene.

ABSTRACT

OBJECTIVE: This study aims to assess the effects of low-dose benzene on DNA damage and O6-methylguanine-DNA methyltransferase (MGMT) methylation in occupational workers. MATERIALS AND METHODS: We recruited 96 nonsmoking male petrochemical industry workers exposed to low-dose benzene and 100 matched control workers. Urinary S-phenylmercapturic acid (SPMA) and S-benzylmercapturic acid (SBMA) were measured for indicating internal exposure of benzene and toluene. The degree of DNA damage was determined by the Comet assay. The levels of MGMT methylation were detected quantitatively by bisulphite-PCR pyrosequencing assay. RESULTS: The benzene-exposed workers had significantly higher levels of urinary SPMA, degree of DNA damage but decreased MGMT methylation than the controls (all p < 0.05). In contrast, the level of urinary SBMA does not differ between benzene-exposed workers and the controls. In all participants, MGMT methylation was negatively associated with the urinary SPMA and the degree of DNA damage, indicating that epigenetic regulation might be involved in response to low-dose benzene exposure-induced genetic damage. DISCUSSION AND CONCLUSION: MGMT methylation could be a potent biomarker associated with low-dose benzene exposure and benzene-induced DNA damage.