[Inhibition of the pathway of benzo (a) pyrene-induced cell cycle changes by all-trans retinoic acid in lung fibroblast].
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.
Jia
Xiao-wei
XW
National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Liu
Bing-ci
BC
Shi
Xiang-lin
XL
Gao
Ai
A
You
Bao-rong
BR
Ye
Meng
M
Shen
Fu-hai
FH
Du
Hong-ju
HJ
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*
C530104:CCND1 protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D019938:Cyclin D1; D001564:Benzo(a)pyrene; D014212:Tretinoin