Hypermethylation of O6-methylguanine-DNA methyltransferase in human bronchial epithelial cell induced by organic extracts of coke oven emissions

This study investigated the mechanism of carcinogenesis induced by coke ovens by investigating the cell genetic damage index and the methylation of O6-methylguanine-DNA methyltransferase (MGMT). The human bronchial epithelial cell 16HBE was treated by 1 íM B(a)P for 48 h, and then was exposed continuously to either 1 ‰ 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 íg/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. Compared with the control group (DMSO), there was a significant hypermethylation in all study groups, along with the suppression of mRNA and protein m a dose-dependent manner, and the gradation ratio was 1.0, 0.96, 0.96, 0.85, 0.32 and 1.0, 1.0, 1.1, 0.41, 0.52, respectively. 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) and (11.67 ( 1.88). The index of DNA damage was negatively correlated to the expression of MGMT mRNA and its protein. The authors concluded that the DNA damage induced by COE might be associated with the suppression of MGMT caused by its hypermethylation.

Authors: Ma, Junxiang; Duan, Huawei; Huang, Chuanfeng; Yang, Haijun; Dai, Yufei; Niu, Yong; Bin, Ping; Liu, Qing; Zheng, Yuxin ;Full Source: Zhonghua Yufang Yixue Zazhi 2011, 45(5), 399-403 (Ch) ;