title: Role of poly(ADP-ribose) glycohydrolase silencing in DNA hypomethylation induced by benzo(a)pyrene.
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.
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China; Department of Preventive Medicine, Gannan Medical College, Jiangxi, China.
authors.forename: Gonghua
authors.initials: G
authors.lastname: Hu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xia
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Yinpin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China. Electronic address: zxzhuang2013@126.com.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D060846:Cell Engineering; D002460:Cell Line; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D002273:Carcinogens; D034741:RNA, Small Interfering; D011064:Poly Adenosine Diphosphate Ribose; D001564:Benzo(a)pyrene; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase
keywords: Benzo(a)pyrene; DNA methylation; Human bronchial epithelial (16HBE) cells; Poly(ADP-ribose) glycohydrolase; Poly(ADP-ribosyl)ation