DNA damage, apoptosis and C-myc, C-fos, and C-jun overexpression induced by selenium in rat hepatocytes.
- Author:
Ri-An YU
1
;
Cheng-Feng YANG
;
Xue-Min CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; Blotting, Northern; Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Genes, fos; drug effects; genetics; Genes, jun; drug effects; genetics; Genes, myc; drug effects; genetics; Hepatocytes; drug effects; pathology; Male; Nucleic Acid Hybridization; Rats; Rats, Sprague-Dawley; Selenium; pharmacology; Sodium Selenite; pharmacology
- From: Biomedical and Environmental Sciences 2006;19(3):197-204
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo study the effects of selenium on DNA damage, apoptosis and c-myc, c-fos, and c-jun expression in rat hepatocytes.
METHODSSodium selenite at the doses of 5, 10, and 20 micromol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was detected by single cell gel electrophoresis (or comet assay). Hepatocellular apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) and flow cytometry. C-myc, c-fos, and c-jun expression in rat hepatocytes were assayed by Northern dot hybridization. C-myc, c-fos, and c-jun protein were detected by immunohistochemical method.
RESULTSAt the doses of 5, 10, and 20 micromol/kg, DNA damage was induced by sodium selenite in rat hepatocytes and the rates of comet cells were 34.40%, 74.80%, and 91.40% respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the doses of sodium selenite (r=0.9501, P<0.01). Sodium selenite at the doses of 5, 10, and 20 micromol/kg caused c-myc, c-fos, and c-jun overexpression obviously. The positive brown-yellow signal for proteins of c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in selenium-treated rat livers. Apoptotic rates (%) of selenium-treated liver cells at the doses of 5, 10, and 20 micromol/kg were (3.72 +/- 1.76), (5.82 +/- 1.42), and (11.76 +/- 1.87) respectively, being much higher than those in the control. Besides an obvious dose-response relationship between apoptotic rates and the doses of sodium selenite (r=0.9897, P<0.01), these results displayed a close relationship between DNA damage rates and apoptotic rates, and the relative coefficient was 0.9021, P<0.01.
CONCLUSIONSelenium at 5-20 micromol/kg can induce DNA damage, apoptosis, and overexpression of c-myc, c-fos, and c-jun in rat hepatocytes.