5'UTR methylation in different genes from workers exposed to volatile organic compounds: A new insight for considering an epigenetic mark as a functional correlate.

Gene-specific methylation has been related with transcriptional/translational consequences in different cells; also, this epigenetic modification is affected by environmental exposures. In previous studies, CYP2E1 activity in toluene-exposed workers was decreased compared to controls, however, CYP2E1 promoter methylation levels did not show significant differences. Here, we compared gene-specific methylation levels at the 5'UTR region, in a subset of workers whom already participated in two former studies, compared to controls. METHODS: DNA was obtained from whole blood in five different groups: occupationally exposed to a mixture of volatile organic compounds (VOC): high levels (n = 19); low levels (n = 19) and very low levels (n = 17), toluene-exposed workers (n = 19) and control group (n = 19). We performed PCR-pyrosequencing at the 5'UTR region from four genes: CYP2E1, IL-6, SOD1 and TNF-α. RESULTS: In participants exposed to high levels of a VOC mixture, we found significant differences: lower methylation levels for IL-6, and higher methylation levels for TNF-α compared to controls. In toluene-exposed workers, we found significant, lower methylation levels for CYP2E1 compared to controls. CONCLUSION: Lower methylation levels at the 5'UTR region from CYP2E1 in toluene exposed-workers, suggests that this epigenetic modification could represent a functional correlate regarding enzymatic activity, as a response to toluene biotransformation.

Possible role of n-hexane as an endocrine disruptor in occupationally exposed women at reproductive age.

Human exposure to n-hexane has been associated with subfertility and, experimentally, with a decrease in follicular development. In order to assess occupational exposure to n-hexane on ovarian function and gonadotropic hormones, we studied Mexican women labouring in a leather shoe factory (n = 34). Individual environmental levels for seven solvents, n-hexane included, were measured; also, urinary 2,5-hexanedione (2,5-HD) was determined. For ovarian function and hormonal status, FSH, LH, oestradiol and anti-Müllerian hormone (AMH) levels were determined. We performed all determinations also in a reference group, administrative workers with no exposure to solvents (n = 32). Results: N-hexane and urinary 2,5-HD levels were higher in exposed group (p < 0.001). More cases of oligomenorrhea as well as longer time for getting pregnant were observed in exposed women compared with controls; a positive association was found between menstrual cycle length and "time for getting pregnant" (p = 0.010); significant associations between FSH serum levels and 2,5-HD urinary levels (post-shift sample) were observed in non-smokers participants presenting oligomenorrhea from exposed group. Also, we found a trend for lower oestradiol levels in exposed participants with current smoking habit (p = 0.059). Conclusions: 2,5-HD urinary levels are associated with decreased gonadotropins levels; hence, n-hexane should be considered an endocrine disruptor in reproductive-age women.