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Vitamin C inhibits benzo[a]pyrene-induced cell cycle changes partly via cyclin D1/E2F pathway in human embryo lung fibroblasts.
- Source :
-
Biomedical and environmental sciences : BES [Biomed Environ Sci] 2006 Jun; Vol. 19 (3), pp. 239-44. - Publication Year :
- 2006
-
Abstract
- Objective: To study the molecular mechanism of the inhibitory effects of vitamin C on benzo[a]pyrene (B[a]P)-induced changes of cell cycle in human embryo lung fibroblast (HELF) cells.<br />Methods: The stable transfectants, HELF transfected with antisense cyclin D1 and antisense CDK4, were established. Cells were cultured and pretreated with vitamin C before stimulation with B[a]P for 24 h. The expression levels of cyclin D1, CDK4, E2F1, and E2F4 were determined by Western blot. Flow cytometric analysis was employed to detect the distributions of cell cycle.<br />Results: B[a]P significantly elevated the expression levels of cyclin D1, E2F1, and E2F4 in HELF cells. Vitamin C decreased the expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-stimulated HELF cells. Dose-dependent relationships were not found between the different concentrations of vitamin C (10, 100, 500, 1000, and 5000 micromol/L) and the expression levels of cyclin D1, E2F1, and E2F4 in HELF cells. The expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-treated transfectants were lower than those in B[a]P-treated HELF cells. The expression levels of cyclin D1 and E2F4 treated with vitamin C and antisense cyclin D1 were decreased compared with those treated with antisense cyclin D1 alone. The effects of vitamin C combined with antisense CDK4 on the expression levels of cyclin D1 and E2F1/E2F4 were similar to those of antisense CDK4 alone. B[a]P progressed HELF cells from G1 to S phase. Both vitamin C and antisense cyclin D1 suppressed the changes of cell cycle progressed by B[a]P. However, antisense CDK4 did not attenuate the above changes. Vitamin C combined with antisense CDK4 markedly suppressed B[a]P-induced changes of cell cycle as compared with antisense CDK4. But the inhibitory effects of vitamin C combined with antisense cyclin D1 on B[a]P-induced changes of cell cycle were similar to those of vitamin C alone or antisense cyclin D1 alone.<br />Conclusions: B[a]P progressed HELF cells from G1 to S phase via intracellular signaling pathway of cyclin D1/E2F. Vitamin C may modulate this signaling pathway to protect cells from injury caused by B[a]P.
- Subjects :
- Blotting, Western methods
Cell Cycle physiology
Cells, Cultured
Cyclin-Dependent Kinase 4 metabolism
Dose-Response Relationship, Drug
Fibroblasts cytology
Fibroblasts metabolism
G1 Phase drug effects
G1 Phase physiology
Humans
Lung embryology
RNA, Antisense genetics
S Phase drug effects
S Phase physiology
Transfection methods
Ascorbic Acid pharmacology
Benzo(a)pyrene
Cell Cycle drug effects
Cyclin D1 metabolism
E2F1 Transcription Factor metabolism
Fibroblasts drug effects
Lung cytology
Subjects
Details
- Language :
- English
- ISSN :
- 0895-3988
- Volume :
- 19
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biomedical and environmental sciences : BES
- Publication Type :
- Academic Journal
- Accession number :
- 16944783