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Toxicol Appl Pharmacol. 2015 Aug 1;286(3):207-15. doi: 10.1016/j.taap.2015.04.016. Epub 2015 May 9.

CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit.

Author information

1
Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato, Mexico. Electronic address: ojimenezgarza@ugto.mx.
2
Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
3
Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato, Mexico.
4
Environmental Toxicology and Pollution Laboratory, Nayarit Autonomous University, Av. Ciudad de la Cultura s/n, "Amado Nervo", Tepic, Nayarit C.P. 63155, Mexico.
5
Department of Toxicology, CINVESTAV, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, 07360 Mexico DF, Mexico.

Abstract

BACKGROUND:

CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated.

GOAL:

To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure.

METHODS:

We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes.

RESULTS:

In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, p<0.05), as well as for IL6 promoter methylation levels (r=.44, p<0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p=0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r=-.37, p<0.05 and r=-.34, p<0.05 respectively).

CONCLUSION:

These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression.

KEYWORDS:

CYP2E1; GSTP1; Gene-specific DNA methylation; SOD1; Smoking habit; Toluene exposure

PMID:
25963742
DOI:
10.1016/j.taap.2015.04.016
[Indexed for MEDLINE]

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