Hypermethylation of O(6)-methylguanine-DNA methyltransferase in human bronchial epithelial cell induced by organic extracts of coke oven emissions / 中华预防医学杂志

<p><b>OBJECTIVE</b>To elucidate the mechanism of carcinogenesis induced by coke oven emissions by investigating the cell genetic damage index and the methylation of O⁶-methylguanine-DNA methyltransferase (MGMT).</p><p><b>METHODS</b>The human bronchial epithelial cell 16HBE was treated by 1 µmol/L B(a)P for 48 h, and then was exposed continuously to either 1‰ dimethyl sulfoxide (DMSO) or organic extracts of coke oven emission (OE-COE) for five days at the concentrations of 0, 2.5, 5.0, 10.0 and 20.0 µg/ml. The methylation-specific PCR (MSP-PCR), RT-PCR and immunoblotting were applied to detect the methylation status, changes of mRNA and protein of MGMT, respectively. Single cell gel electrophoresis was used to detect DNA damage induced by OE-COE.</p><p><b>RESULTS</b>Compared with the control group (DMSO), there was a significant hypermethylation in all study groups, along with the suppression of mRNA and protein in a dose-dependent manner, and the gradation ratio of them was 1.0, 0.96, 0.96, 0.85, 0.32 and 1.0, 1.0, 1.1, 0.41, 0.52, separately. There was a significant DNA damage with a dose-effect relationship in all study groups (F = 41.22, P < 0.05), and the comet Olive tail moment was (2.98 ± 1.43), (4.76 ± 1.79), (10.09 ± 1.75), (11.38 ± 1.77), (11.67 ± 1.88). The further study found that the index of DNA damage was negatively correlated to the expression of MGMT mRNA and its protein.</p><p><b>CONCLUSION</b>The DNA damage induced by COE might be associated with the suppression of MGMT caused by its hypermethylation.</p>

Effect of genetic polymorphisms of microsomal epoxide hydrolase on urinary 1-hydroxypyrene levels in coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers.</p><p><b>METHODS</b>One hundred and forty-eight workers from a coke oven plant and 69 controls without occupational PAHs exposure were selected in this study. Urinary 1-hydroxypyrene was detected by high performance liquid chromatography with florescence detector. The genotypes at I462V site in exon 7 of CYP1A1 gene, GSTM1, GSTT1, I105V site in GSTP1gene, Pst1 and Dra1 sites in CYP2E1 gene, P187S site in NQO1 gene, Kpn1, BamH1 and Taq1 sites in NAT2 gene, and H113Y, R139H sites in mEH gene were determined by PCR-based methods. Personal information including occupational exposure history, age, sex, smoking and drinking status was collected by the questionnaire.</p><p><b>RESULTS</b>The level of urinary 1-hydroxypyrene in coke oven workers [(5.61 +/- 1.04) mol/mol Cr] was higher than that in control [(0.74 +/- 0.32) micro mol/mol Cr]. After adjusting external occupational exposure category and smoking, coke oven workers with variant homozygotes at H113Y site of mEH gene had significantly higher urinary 1-hydroxypyrene concentrations than those with heterozygotes, and wild homozygotes (6.41 +/- 1.09 vs. 6.24 +/- 1.08, and 4.62 +/- 0.95 micro mol/mol Cr, P < 0.05), and gene-gene interaction was found between CYP1A1 and mEH.</p><p><b>CONCLUSION</b>Genetic polymorphism of mEH gene could be a susceptible biomarker in coke oven workers which was involved in the individual susceptibility on metabolism of PAHs.</p>