HBV转基因小鼠的解毒活力变化的研究  

DECREASED DETOXIFICATION OF AFLATOXIN B1 IN HEPATITIS B VIRUS TRANSGENIC MICE

作　　者：励雁峰[1,2,3] 吴万垠[1,2,3] 张学理[1,2,3] 成国祥 马积庆[1,2,3] 顾健人 钱耕荪[1,2,3] 

机构地区：[1]上海市肿瘤研究所 [2]上海医科大学肿瘤医院 [3]扬州大学农学院

出　　处：《肿瘤》1997年第4期187-189,共3页Tumor

基　　金：国家自然科学基金癌基因和相关基因国家重点实验室基金资助国家九.五攻关基金

摘　　要：ＡＦＢ１和ＨＢＶ是致肝癌的两个主要因素。研究表明ＡＦＢ１与ＨＢＶ有协同致肝癌作用，但其机理不明。方法利用ＨＢＶ转基因小鼠模型，分析小鼠肝脏组织中的细胞色素Ｐ４５０酶的含量和活性，ＧＳＨ和ＧＳＴ的含量和活性，并测定ＨＢＶ转基因小鼠暴露于ＡＦＢ１后血清ＡＦＢ１┐白蛋白加成物的含量。结果加成物的含量在ＨＢＶ转基因小鼠都较对照小鼠高，细胞色素Ｐ４５０酶含量明显降低而活性有所上升，ＧＳＨ含量和ＧＳＴ酶活性都明显下降。结论ＨＢＶ转基因小鼠的解毒代谢能力下降。ＨＢＶ影响了小鼠的解毒代谢，使小鼠对ＡＦＢ１敏感。Aflatoxin B1 (AFB1)is activated to form AFB1 8,9 epoxide via cytochrome P450s.The epoxide can then be rendered innocuous via phase 2 enzymes(glutathione S transferases GSTs). The mechanistic role of human hepatitis B viurs(HBV) in liver tumorigenesis is unresolved.Methods:To determine whether HBV transgenic mice are more susceptible to the effects of AFB 1,livers from transgenic and control non transgenic mice were analyzed for the enzyme systems involved in metabolism. Results: The levels of liver cytochrome P450s and GSH and the activity of GSTs of the transgenic mice were significantly lower than nontransgenic mice( P <0 01).The activities of cytochrome P450 enzymes in the livers of transgenic mice were higher than those of non transgenic mice.After exposure to AFB1, the content of AFB1 albumin adducts in the sera of transgenic mice were higher than those of non transgenic mice at multiple timepoints over 24 hours. Conclusions:These data suggest that HBV decreases detoxification of AFB1 in the transgenic mice and are consistent with the synergy observed between HBV expression and hepatocarcinogenesis in animal models and epidemiological studies.

关 键 词：代谢解毒 黄曲霉毒素 HBV 肝肿瘤 

分 类 号：R735.702[医药卫生—肿瘤]