【作者】 石远； 崔仑标； 戴贵东； 宋玲； 王心如；

【Author】 SHI Yuan, CUIlun-Biao, DAI Gui-Dong, SONG Lin, WANG Xin-Ru(Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China)

【机构】 南京医科大学应用毒理研究所；

【摘要】 [目的]探讨对苯二甲酸(terephthalic acid,TPA)诱导雄性大鼠膀胱癌前病变可能的分子机制。[方法]大鼠随机分为4组,分别饲喂0%,0.2%,1%和5%TPA,饲养90天后宰杀,收集膀胱标本进行组织病理分析,用免疫组织化学的方法分析膀胱上皮增殖细胞核抗原(PCNA)和细胞周期蛋白p16ink4a、cyclinD1、CDK4的表达,聚合酶链式反应-单链构象多态性(PCR-SSCP)分析p16基因突变。[结果]增生膀胱上皮PCNA阳性表达显著高于对照组(P<0.01),cyclin D1和CDK4出现过表达,p16Ink4a表达减少和缺失,p16基因未发生突变。[结论]p16Ink4a-cyclin D1/CDK4通路功能异常可能是对苯二甲酸致大鼠膀胱癌前病变的重要分子机制。更多还原

【Abstract】 [Objective] The purpose was to investigate the molecular mechanism of bladder precancerous lesion induced by terephthalic acid in male rat. [Methods] male rats were orally administered TPA in diet at the levels 0(control),0.2, 1, 5%. After 90-day, bladder samples were collected for histopathological diagnosis. Immunohistochemical method was used to characterize the expression of p16ink4a, cyclin D1, CDK4 in relation to that of proliferating cell nuclear antigen (PCNA) in bladder. Mutation of p16 gene was detected by PCR-SSCP. [Results] PCNA-postive focal hyperplasic lesions were detected in all epithelial layers. Over expressions of cyclin D1, CDK4 were found in the corresponding lesion .P16lnk4a nuclear staining reduced in proliferative bladder(14/52).NO mutation of p16 gene was found. [Conclusion] Functional abnormality of p16ink4a-cyclin D1/CDK4 pathway may be important Molecular mechanism of bladder precancerous lesion induced by terephthalic acid in male rat更多还原