title: [Inhibition of the pathway of benzo (a) pyrene-induced cell cycle changes by all-trans retinoic acid in lung fibroblast].
abstract: OBJECTIVE
  To investigate the reverse effect of all-trans retinoic acid (ATRA) on Benzo (a) pyrene (B (a) P)-induced cyclin D1, CDK4, E2F-1 and E2F-4 expression and cell cycle progression in human embryo lung fibroblast (HELF).
  
  
  METHODS
  After HELF cells was treated with ATRA, they were exposed to 2 micromol/L of B (a) P. Western blotting was employed to detect protein expression level; the RNA transfection techniques was used to investigate ATRA-induced signal pathway; flow cytometry was used to detect cell cycle progression.
  
  
  RESULTS
  After treatment with 2 micromol/L B (a) P for 24 h, the expression of cyclin D1 and E2F-1 were both increased significantly in HELF; the expression of E2F-4 and CDK4 were not changed markedly; pretreatment with 0.1 micromol/L ATRA for 24 h could efficiently decrease B (a) P-induced overexpression of cyclin D1 and E2F-1; stimulation to antisense cyclin D1 or antisense CDK4 by B (a) P could significantly impair E2F-1 up-regulation; pretreatment with ATRA, cells with antisense cyclin D1 or antisense CDK4 showed a less decrease in B (a) P-induced overexpression of E2F-1 compared to similarly treated control cells; flow cytometry analysis showed B (a) P promoted cell cycle progression from G(1) phase to S phase, while pretreatment with ATRA could inhibit B (a) P-induced cell cycle progression by an accumulation of cells in the G(1) phase.
  
  
  CONCLUSIONS
  ATRA could block B (a) P-induced cell cycle promotion through cyclin D1/E2F-1 pathway in HELF.
authors.affiliation: National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Xiao-wei
authors.initials: XW
authors.lastname: Jia
authors.forename: Bing-ci
authors.initials: BC
authors.lastname: Liu
authors.forename: Xiang-lin
authors.initials: XL
authors.lastname: Shi
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
authors.forename: Bao-rong
authors.initials: BR
authors.lastname: You
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Fu-hai
authors.initials: FH
authors.lastname: Shen
authors.forename: Hong-ju
authors.initials: HJ
authors.lastname: Du
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C530104:CCND1 protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D019938:Cyclin D1; D001564:Benzo(a)pyrene; D014212:Tretinoin