Gene-specific 5’-UTR methylation vs. promoter methylation in leukocytes from workers exposed to different levels of VOCs.

Abstract

Introduction: As a result of exposure to toxic substances, different human and animals cells have displayed either global DNA hypomethylation or gene-specific hypermethylation. Specifically in occupational volatile organic compound (VOC) exposure, we previously found hypermethylation in TOP2A, SOD1 and TNF-a promoter area in leukocytes from people exposed to a complex VOC mixture, while participants exposed to a single VOC did not show any differences compared to controls. The aim of this study was to analyze the methylation pattern in the 5’-UTR region, considered for some authors as an “internal/alternative promoter area” in people occupationally exposed to a single VOC compared to VOC mixtures exposure as well as a reference, non-exposed group. Methods: PCR-pyrosequencing was performed in order to analyze methylation status in CpG’s located at the 5’-UTR region of the TOP2A, SOD1, IL6, TNF-a and CYP2E1 genes in leukocytes from Mexican workers laboring at three different scenarios with VOC exposure compared to a reference group. Results: 5’-UTR region from IL6 and TOP2A genes showed hypomethylation for two populations exposed to a VOC mixture, while TNF-a showed hypermethylation; methylation in the SOD1 gene did not show differences between groups. DNA obtained from the reference group showed hypermethylation in the 5’-UTR region from the CYP2E1 gene compared to all exposed subgroups. Conclusions: 5’-UTR region in certain genes is more prone to undergo epigenetic modifications compared to promoter area as a result of VOC exposure. 5’-UTR methylation status must be considered in a near future as an early biomarker of effect in human chemical toxicity.