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Reference Promoter methylation status in genes related with inflammation, nitrosative stress and xenobiotic metabolism in low-level benzene exposure: Searching for biomarkers of oncogenesis.

Authors Jiménez-Garza O, Guo L, Byun HM, Carrieri M, Bartolucci GB, Zhong J, Baccarelli AA.
Institution Health Sciences Division, University of Guanajuato, León Campus, Blvd. Puente del Mienio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato, Mexico. Electronic address: ojimenezgarza@ugto.mx.
Citation Food Chem Toxicol. 2017 Nov;109(Pt 1):669-676.
DOI ID 10.1016/j.fct.2017.08.019
PubMed® ID 28823944
Review Status Is curated Curated.
Abstract Exposure to low levels of benzene may cause acute myeloid leukemia in humans. Epigenetic effects in benzene exposure have been studied for tumor suppressor genes and oxidative stress-related genes, but other cellular pathways must be explored. Here, we studied promoter DNA methylation of IL6, CYP2E1 and iNOS in blood cells from three groups of workers: a) gas station attendants (GS) exposed to low levels of benzene; b) plastic shoe factory workers (PS) exposed to other solvents different to benzene and c) administrative workers as a reference group with no solvent exposure (C).

RESULTS: IL6 promoter methylation was higher in GS workers (p < 0.05). Also in GS, CYP2E1 promoter methylation negatively correlated with benzene levels (r = -0.47, p < 0.05); iNOS promoter methylation positively correlated with CYP2E1 promoter methylation (r = 0.29, p < 0.05), cumulative time of exposure (r = 0.31, p < 0.05) as well as with urinary levels of S- Phenyl mercapturic acid (SPMA), (r = 0.55, p < 0.05). Our results demonstrate alterations in the inflammation pathway at the epigenetic level associated with exposure to benzene. Correlations between iNOS methylation with both CYP2E1 methylation and urinary SPMA levels represent novel evidence about CYP2E1 epigenetic regulation and activity related with nitrosative stress, making promoter methylation status of these genes a potential biomarker in early stages of oncogenesis.