氯乙烯致大鼠DNA损伤与DNA损伤修复酶和p53蛋白的表达

目的研究氯乙烯（VC）对大鼠原代肝细胞DNA的损伤作用，及对DNA损伤修复酶（rMSH2和XPD）和抑癌蛋白p53表达的影响；探索VC所致DNA损伤的修复和调控机制。方法大鼠腹腔注射VC，隔日染毒，染毒剂量分别为5，10和20mg／kg。单细胞凝胶电泳测肝细胞DNA损伤，免疫组化法测肝脏DNA损伤修复酶的表达。结果彗星细胞数目随染毒剂量增加而增加，彗星发生率与VC染毒剂量问存在明显的相关关系。rMSH2表达随染毒剂量增加而减少．XPD和p53的表达随染毒剂量增加而增加。VC致DNA损伤与XPD表达具有相关关系。结论VC可导致肝细胞DNA发生损伤，且存在剂量一反应关系；DNA损伤修复酶和p53蛋白参与修复VC所致的DNA损伤。

Vinyl Chloride Induced DNA Damage and Expressions of p53 and DNA Damage Repair Enzyme in Rats

Objective To investigate vinyl chloride(VC)induced DNA damage of liver cells of rats,to examine the changes of expressions of DNA damage repair enzymes(rMSH2 and XPD)and the tumor suppressor protein(p53),and to explore the repair and modulation mechanism of DNA damage searching for early sensitive indexes of detecting these damages.Methods VC was intraperitoneally administrated to rats with dosages of 5,10,and 20 mg/kg.DNA damage of liver cells was detected by single cell gel electrophoresis.The expressions of DNA damage repair enzymes were measured by immunohistochemical methods.Results The numbers of comet cells in the experimental groups were significantly different from those of the control.The ratios of comet cells were correlated with the doses of VC.The expressions of rMSH2 decreased with the doses increase of VC,and had significant difference;XPD and p53 increased with the dose of VC.DNA damages had association with the expressions of XPD.Conclusions VC could induce DNA damage of lymphocytes of rats,a dose-response relationship was observed between exposure doses of VC and DNA damage.DNA damage repair exzymes and tumor suppressor protein(p53)took part in the repair of the DNA damages induced by VC.