The prevalence and persistence of aberrant promoter DNA methylation in benzene-exposed Chinese workers

Abstract

Aberrant DNA methylation patterns are common in cancers and environmental pollutant exposed subjects. Up to date, few studies have examined the aberrant DNA methylation patterns in benzene exposed workers. We recruited 141 benzene-exposed workers, including 83 benzene-exposed workers from a shoe factory in Wenzhou and 58 workers from a painting workshop in Wuhu, 35 workers in Wuhu were followed from 2009 to 2013, and 48 indoor workers as controls from Wenzhou. We used high-resolution melting (HRM) to quantitate human samples of DNA methylation in long interspersed nuclear element-1 (LINE-1), (6)-methylguanine-DNA methyltransferase (MGMT), and DNA mismatch repair gene human mutator L homologue 1 (hMLH1). AML-5 cells were treated with benzoquinone (BQ) and hydroquinone (HQ), and the promoter methylation of MGMT and hMLH1 was detected using the bisulfite sequencing PCR method. The degree of LINE-1 methylation in benzene-exposed workers was significantly lower than that of the controls ( p <0.001), and the degree of MGMT ( p <0.001) and hMLH1 ( p = 0.01) methylation was significantly higher than that of the controls. The in vitro study validated the aberrant hypermethylation of hMLH1 after treatment with BQ. Among the cohort workers who were followed from 2009 to 2013, the LINE1 methylation elevated in 2013 than 2009 ( p = 0.004), and premotor methylation in hMLH1 reduced in 2013 than 2009 ( p = 0.045) with the reduction of the benzene exposure. This study provides evidence that benzene exposure can induce LINE-1 hypomethylation and DNA repair gene hypermethylation.

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

“…In addition to genotoxic modifications, acquired epigenetic alterations may participate in benzene leukemogenesis [ 109 , 110 , 111 ], and numerous findings are more coherent with an epigenetic model for onset of benzene-AML in which modified homeostatic control in the BM niche, not cytogenetic damage, prevails in the initial elaboration of the leukemic stem cell phenotype, a system completely different from preceding models of clonal cytogenetic damage [ 112 ].…”

Linking Environmental Exposures to Molecular Pathogenesis in Non-Hodgkin Lymphoma Subtypes

“…Compromising the activity of DNA damage repair proteins leads to genomic instability (57,58), thus setting the stage for oncogenesis. In a study that measured benzene concentrations and methylation patterns of genes implicated in carcinogenesis in peripheral blood, investigators found a higher degree of methylation in the promotor region of MGMT in healthy, benzene-exposed workers compared with healthy, unexposed workers (59). As mentioned previously, certain SNPs in MGMT have been shown to interact with chlorinated solvent exposure to increase DLBCL risk, highlighting this gene as a key suspect in chemical exposure-mediated lymphomagenesis whose dysregulation may occur via several distinct mechanisms.…”

Promoter hypermethylation in CSF3R induces peripheral neutrophil reduction in benzene‐exposure poisoning

“…This finding illustrates that the genetic damage induced by benzene exposure is still serious, even after leaving a benzene work environment. Consistent with our previous reports (Ren et al ., 2019), the workers had a high MN frequency after the benzene concentration was significantly reduced in a follow‐up study.…”