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.
Highlights
Benzene is a ubiquitous environmental and occupational pollutant that has been classified as a Group 1 carcinogen by IARC (IARC 1982)
We focus on the global DNA methylation surrogated by the level of long interspersed nucleotide element-1 (LINE–1) methylation and on the promoter regions in DNA repair genes, indicated as O6-methylguanine-DNA methyltransferase (MGMT), and human mismatch-repair gene
Significant decreases in WBC, RBC and platelet counts and increases in MN frequency have been observed in human populations exposed to relatively high or low levels of benzene[26, 28, 29]
Summary
Benzene is a ubiquitous environmental and occupational pollutant that has been classified as a Group 1 carcinogen by IARC (IARC 1982). It is well known that chronic poisoning caused by benzene still occurs in both Western countries and in China, and it remains significant as a high number of leukemia patients has been reported in recent years [1,2,3]. It is generally accepted that cancer arises from genetic and epigenetic errors induced by environmental pollutants. The methylation of cytosines allows the encoding of heritable epigenetic information directly onto the DNA while leaving the DNA nucleotide sequence intact, and its role in carcinogenesis has become a topic of considerable interest in the last few years [5]. More attention is being paid to environmental pollution-induced alterations of DNA methylation, including global hypomethylation, gene-specific hypermethylation or the hypomethylation of specific genes
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