| Literature DB >> 25195819 |
Haiyan Huang1, Gonghua Hu2, Jianfeng Cai1, Bo Xia1, Jianjun Liu1, Xuan Li1, Wei Gao1, Jianqing Zhang1, Yinpin Liu1, Zhixiong Zhuang3.
Abstract
Benzo(a)pyrene (BaP) is a known carcinogen cytotoxic which can trigger extensive cellular responses. Many evidences suggest that inhibitors of poly(ADP-ribose) glycohydrolase (PARG) are potent anticancer drug candidates. However, the role of PARG in BaP carcinogenesis is less understood. Here we used PARG-deficient human bronchial epithelial cell line (shPARG cell) as an in vitro model, and investigated the role of PARG silencing in DNA methylation pattern changed by BaP. Our study shows, BaP treatment decreased global DNA methylation levels in 16HBE cells in a dose-dependent manner, but no dramatic changes were observed in shPARG cells. Further investigation revealed PARG silencing protected DNA methyltransferases (DNMTs) activity from change by BaP exposure. Interestingly, Dnmt1 is PARylated in PARG-null cells after BaP exposure. The results show a role for PARG silencing in DNA hypomethylation induced by BaP that may provide new clue for cancer therapy.Entities:
Keywords: Benzo(a)pyrene; DNA methylation; Human bronchial epithelial (16HBE) cells; Poly(ADP-ribose) glycohydrolase; Poly(ADP-ribosyl)ation
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Year: 2014 PMID： 25195819 DOI： 10.1016/j.bbrc.2014.08.146
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575