Effects of Cadmium on Hepatocellular DNA Damage,Proto-Oncogene Expression and Apoptosis in Rats  

作　　者：RI-AN YU LING-FEI HE XUE-MIN CHEN 

机构地区：[1]Department of Occupattonal an Environmental Health, Shool of Public Health, Guangdong Pharmaceutical University,Guangzhou 510310, Guangdong, China [2]The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510080, Guangdong, China [3]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 430030, Hubei, China

出　　处：《Biomedical and Environmental Sciences》2007年第2期146-153,共8页生物医学与环境科学（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China (No. 30271110).

摘　　要：Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.

关 键 词：CADMIUM DNA damage PROTO-ONCOGENE APOPTOSIS 

分 类 号：X503.22[环境科学与工程—环境工程] R995[医药卫生—毒理学]