title: Poly(ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Benzo(a)pyrene Induced Cell Transformation.
abstract: Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant and known carcinogen, which can induce malignant transformation in rodent and human cells. Poly(ADP-ribose) glycohydrolase (PARG), the primary enzyme that catalyzes the degradation of poly(ADP-ribose) (PAR), has been known to play an important role in regulating DNA damage repair and maintaining genomic stability. Although PARG has been shown to be a downstream effector of BaP, the role of PARG in BaP induced carcinogenesis remains unclear. In this study, we used the PARG-deficient human bronchial epithelial cell line (shPARG) as a model to examine how PARG contributed to the carcinogenesis induced by chronic BaP exposure under various concentrations (0, 10, 20 and 40 μM). Our results showed that PARG silencing dramatically reduced DNA damages, chromosome abnormalities, and micronuclei formations in the PARG-deficient human bronchial epithelial cells compared to the control cells (16HBE cells). Meanwhile, the wound healing assay showed that PARG silencing significantly inhibited BaP-induced cell migration. Furthermore, silencing of PARG significantly reduced the volume and weight of tumors in Balb/c nude mice injected with BaP induced transformed human bronchial epithelial cells. This was the first study that reported evidences to support an oncogenic role of PARG in BaP induced carcinogenesis, which provided a new perspective for our understanding in BaP exposure induced cancer.
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: School of Public Health, Guangxi Medical University, Guangxi, China.
authors.forename: Xiyi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Occupational Disease Prevention, Baoan Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Peiwu
authors.initials: P
authors.lastname: Huang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Guangdong, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Zhuang
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: 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: 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.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics; D006026:Glycoside Hydrolases / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D001564:Benzo(a)pyrene; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase