title: [Role of PARP-1 in formaldehyde-induced DNA damage repair and apoptosis in human bronchial epithelial cells].
abstract: OBJECTIVE
  To study the role of poly (ADP-ribose) polymerase-l (PARP-1) in formaldehyde-induced DNA damage response in human bronchial epithelial (HBE) cells and to investigate the mechanism of formaldehyde carcinogenicity.
  
  
  METHODS
  The protein levels were measured by Western blot. The interaction between different proteins was determined by co-immunoprecipitation assay. The chemical inhibitor was used to confirm the relationship between PARP-1 and DNA damage repair.
  
  
  RESULTS
  After being exposed to different concentrations of formaldehyde for 4 h, HBE cells showed no significant changes in cell viability. Cell viability was significantly reduced after 24-h exposure to 80 and 160 µmol/L formaldehyde (P < 0.05). The 10 µmol/L formaldehyde resulted in significant increases in the protein levels of PARP-1 and XRCC-1. However, 80 µmol/L formaldehyde led to a significant decrease in the protein level of PARP-1 of 124 KD molecular weight but a significant increase in the protein level of PARP-1 of 89 KD molecular weight; there was no significant change in the protein level of XRCC-1. The co-immunoprecipitation assay showed that 10 µmol/L formaldehyde induced increased binding between PARP-1 and XRCC-1, but 80 µmol/L formaldehyde led to no significant change in binding between PARP-1 and XRCC-1. Here, we confirmed the role of 10 µmol/L formaldehyde in strand breaks by comet assay which showed an increase in the tail DNA content of HBE cells after 4-h formaldehyde exposure. No significant difference was observed in tail DNA content between treated HBE cells and control cells at 2 h after formaldehyde was removed. Moreover, compared with control, inhibition of PARP-1 induced a significant increase in tail DNA content, and a significant difference was observed in tail DNA content between inhibited HBE cells and control cells at 2 h after formaldehyde was removed. Inhibition of PARP-1 significantly reduced DNA repair capacity.
  
  
  CONCLUSIONS
  PARP-1 mediated the repair of DNA damage induced by low-concentration formaldehyde through recruiting XRCC-1 protein, and may be involved in the regulation of cell apoptosis induced by high-concentration formaldehyde.
authors.affiliation: National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Jia
authors.forename: Xianan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jia
authors.affiliation: E-mail: yxzheng@163bj.com.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D005557:Formaldehyde; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases