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O08-5 Gene-specific 5’-UTR methylation vs. promoter methylation in leukocytes from workers exposed to different levels of volatile organic compounds
  1. Octavio Jiménez-Garza,
  2. Luxana Reynaga-Ornelas,
  3. Adriana Dávalos-Pérez
  1. Health Sciences Division, Universidad De Guanajuato Campus León, León, México

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-α 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 analyse 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 (n = 19) compared to VOC mixtures exposure (n = 20) as well as a reference, non-exposed group (n = 20).

Methods PCR-pyrosequencing was performed in order to analyse methylation status in CpG’s located at the 5’-UTR region of the TOP2A, SOD1, IL6, TNF-α and CYP2E1 genes in leukocytes from Mexican workers labouring 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-α 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.

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