Effect of PARP-1 deficiency on DNA damage and repair in human bronchial epithelial cells exposed to Benzo(a)pyrene.
Benzo[a]pyrene is a ubiquitously distributed environmental pollutant known to cause DNA damage, whereas PARP-1 is a nuclear enzyme that is activated by damaged DNA and plays an important role in base excision repair and genomic stability. Here, 16HBE and its PAPR1-deficient cells were exposed to BaP, and the DNA damage level and repair ability of both cell lines were measured by alkaline comet assay. The results showed that cell viability of both cell lines decreased in a dose-dependent manner when exposed to BaP, but there was no significant difference between two cell lines. Comet assay showed that BaP caused DNA damage in both cell lines at an obvious dose- and time-dependent manner. Compare with 16HBE, the PARP1-deficient cells were more sensitive to the damage caused by BaP. The results of DNA repair experiment showed that both cell lines can recover from the damage in a time-dependent pattern. The relative repair percentage of PARP1-deficient cells were generally lower than that of 16HBE at all exposed concentrations at the early stage of repair, but tended to be closer between two cell lines at the later period. According to results, we came to the conclusion that PARP1-deficient cells were more sensitive to BaP in contrast to normal 16HBE; DNA repair capacity in PARP1-deficient cells decreased significantly at the early stage of repair, but increased to the equivalent level of normal 16HBE in the later period. PARP-1 plays an important role in early repair of DNA damage caused by BaP in 16HBE notwithstanding the main repair work is taken by NER pathway.
Tao
Gong-Hua
GH
Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, Guangdong, People's Republic of China.
Yang
Lin-Qing
LQ
Gong
Chun-Mei
CM
Huang
Hai-Yan
HY
Liu
Jian-Dong
JD
Liu
Jian-Jun
JJ
Yuan
Jian-Hui
JH
Chen
Wen
W
Zhuang
Zhi-Xiong
ZX
D001564:Benzo(a)pyrene / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing; D006801:Humans; D008954:Models, Biological; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics; D034622:RNA Interference; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001564:Benzo(a)pyrene; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases