Promoter methylation status in genes related with inflammation, nitrosative stress and xenobiotic metabolism in low-level benzene exposure: Searching for biomarkers of oncogenesis
| Autor: | Andrea A. Baccarelli, Hyang-Min Byun, Octavio Jiménez-Garza, Giovanni Battista Bartolucci, Mariella Carrieri, Jia Zhong, Liqiong Guo |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Carcinogenesis Toxicology medicine.disease_cause Epigenesis Genetic chemistry.chemical_compound 0302 clinical medicine Neoplasms Promoter Regions Genetic Inhalation Exposure Myeloid leukemia Cytochrome P-450 CYP2E1 General Medicine Methylation Middle Aged CYP2E1 iNOS Occupational benzene exposure Nitrosative Stress 030220 oncology & carcinogenesis Female Gen-specific methylation Adult IL6 Oncogenesis Acetylcysteine Benzene Biomarkers DNA Methylation Humans Inflammation Interleukin-6 Xenobiotics Young Adult Biology Promoter Regions 03 medical and health sciences Genetic medicine Epigenetics Promoter Molecular biology 030104 developmental biology chemistry Solvent exposure Drug metabolism Epigenesis Food Science |
| Zdroj: | Food and Chemical Toxicology. 109:669-676 |
| ISSN: | 0278-6915 |
| DOI: | 10.1016/j.fct.2017.08.019 |
| Popis: | 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).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. |
| Databáze: | OpenAIRE |
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