Aberrant DNA Methylation of Two Tumor Suppressor Genes, p14(ARF) and p15(INK4b), after Chronic Occupational Exposure to Low Level of Benzene

Background: Exposure to benzene would be associated with many diseases including leukemia. Epigenetic alterations seem to be among the main mechanisms involved. Objective: To determine if chronic occupational exposure to low level of benzene would be associated with DNA methylation. Methods: Global DNA methylation and promoter-specific methylation of the two tumor suppressor genes, p14(ARF) and p15(INK4b), were assessed employing methylation-specific PCR using the DNA extracted from 40 petrochemical workers exposed to ambient benzene levels of <1 ppm, and 31 office workers not exposed to benzene or its derivatives. Results: While an increase in global DNA methylation of 5% in p14(ARF) (p=0.501) and 28% in p15(INK4b) (p=0.02) genes was observed in the exposed group, no hypermethylation in either of the studied genes was observed in the unexposed group. No significant association was found between the frequency of aberrant methylation and either of age, work experience, and smoking habit in the exposed group. Conclusion: Chronic occupational exposure to lower than the permissible exposure limit of benzene may still result in DNA methylation of tumor suppressor genes that may ultimately lead to development of cancer.