Inhibition of the pathway of benzo (a) pyrene-induced cell cycle changes by all-trans retinoic acid in lung fibroblast.
- Author:
Xiao-wei JIA
1
;
Bing-ci LIU
;
Xiang-lin SHI
;
Ai GAO
;
Bao-rong YOU
;
Meng YE
;
Fu-hai SHEN
;
Hong-ju DU
Author Information
- Publication Type:Journal Article
- MeSH: Benzo(a)pyrene; toxicity; Cell Cycle; drug effects; Cells, Cultured; Cyclin D1; metabolism; E2F1 Transcription Factor; metabolism; Fibroblasts; cytology; drug effects; metabolism; Flow Cytometry; Humans; Lung; cytology; metabolism; Signal Transduction; drug effects; Tretinoin; pharmacology
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(5):329-332
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSAfter 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.
RESULTAfter 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.
CONCLUSIONATRA could block B (a) P-induced cell cycle promotion through cyclin D1/E2F-1 pathway in HELF.