黄曲霉毒素B_1诱发大鼠肝癌过程中对CYP3A4活性的影响  

Effect of CYP3A4 activity on aflatoxin B_1-induced hepatocarcinogenesis in Wistar rats

作　　者：欧超[1] 郑海平[2] 曹骥[1] 杨春[1] 李瑗[1] 唐艳萍[1] 杨芳[1] 李黄羿[1] 苏建家[1] 

机构地区：[1]广西肿瘤防治研究所实验研究部,南宁530021 [2]广西医科大学第一附属医院肿瘤内科

出　　处：《中国癌症防治杂志》2011年第2期110-113,共4页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：广西科技基金资助项目(桂科基0832009);广西医科大学研究生创新课题(2009105981002M178)

摘　　要：目的探讨黄曲霉毒素B1(AFB1)诱发肝癌过程中对CYP3A4活性的影响。方法采用大鼠肝微粒体混合酶体外代谢体系,利用荧光定量法动态检测AFB1诱发肝癌过程中不同时期CYP3A4酶活性。结果 AFB1组CYP3A4含量从实验开始逐渐升高,至23周达顶峰,然后逐渐降低,到43周又升高,出现双波峰变化,阶段性比较差异有统计学意义(P=0.000);对照组CYP3A4含量在整个实验过程中,除33周和63周出现明显降低外,其他各阶段变化不大;组间比较显示AFB1组在诱癌过程中有抑制CYP3A4的趋势,于63周抑制最明显,但尚未达统计学意义(P=0.638);结论AFB1在诱癌过程中有抑制CYP3A4的趋势,可能是与早期癌变的细胞减少对特定基因毒性物质的活化有关。Objective To investigate the effect of CYP3A4 activity on aflatoxin B1（AFB1）-induced hepatocarcinogenesis in Wistar rats.Methods 45 Wistar rats were grouped randomly into AFB1-teatment（group A） and the control（group B）.Rats in group A were injected with AFB1 through abdomen,1-3 times per week with the dosage 200μg/kg of body weight.Liver biopsies were performed on all animals during the 13th-,23rd-,33rd-,43rd-,53rd-and 63rd-week of the experiment,and the animals were executed at the 73rd-week.CYP3A4 activity was examined on each liver sample by the method of fluorescence quantitation.Results In group A,CYP3A4 activity increased gradually from the beginning of the experiment,reached the highest value at the 23rd-week and then decrease gradually,increased again at the 43rd-week,which formed a double peaks and the differences among the stages were significant（P=0.000）.In group B,CYP3A4 activity decreased significantly at the 33rd-and 63rd-week but little change was observed in the other stages.The most obvious difference between group A and B was at the 63rd-week but the difference was not statistically significant（P=0.638）.Conclusion AFB1 might inhibit the activity of CYP3A4 during the process of hepatocarcinogenesis of rats,by which to promote the resistance of early cancer cells against gene toxicity and then to develop liver cancer.

关 键 词：细胞色素CYP3A4 AFB1 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]