DNA damage, apoptosis and C-myc, C-fos, and C-jun overexpression induced by selenium in rat hepatocytes.
OBJECTIVE
To study the effects of selenium on DNA damage, apoptosis and c-myc, c-fos, and c-jun expression in rat hepatocytes.


METHODS
Sodium 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.


RESULTS
At 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.


CONCLUSIONS
Selenium at 5-20 micromol/kg can induce DNA damage, apoptosis, and overexpression of c-myc, c-fos, and c-jun in rat hepatocytes.
Yu
Ri-An
RA
Department of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. yurian.tj@163.com
Yang
Cheng-Feng
CF
Chen
Xue-Min
XM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics; D016758:Genes, jun / Q000187:drug effects* / Q000235:genetics; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009693:Nucleic Acid Hybridization; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology
D012643:Selenium; D018038:Sodium Selenite