Abstract:
:Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene-induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene-induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene-exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean ± SD: 4.73 ± 3.46% vs. 3.63 ± 1.96%, P = 0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene-exposed workers (P(trend) = 0.001), but not in unexposed controls (P(trend) = 0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P(trend) = 0.044) in benzene-exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (≥6%) of methylation levels in controls and a leucopenia cutoff (<4 × 10(9) /L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Xing C,Chen Q,Li G,Zhang L,Zheng M,Zou Z,Hou L,Wang QF,Liu X,Guo Xdoi
10.1002/em.21786subject
Has Abstractpub_date
2013-07-01 00:00:00pages
397-405issue
6eissn
0893-6692issn
1098-2280journal_volume
54pub_type
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
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pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20401
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850250309
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.20216
更新日期:2006-06-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10188
更新日期:2003-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1031
更新日期:2001-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21702
更新日期:2012-07-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850230209
更新日期:1994-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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更新日期:2018-03-01 00:00:00
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