Overexpression of cytochrome P-450 isoforms involved in aflatoxin B-1 bioactivation in human liver with cirrhosis and hepatitis

被引:54
|
作者
Kirby, GM [1 ]
Batist, G [1 ]
Alpert, L [1 ]
Lamoureux, E [1 ]
Cameron, RG [1 ]
AlaouiJamali, MA [1 ]
机构
[1] MCGILL UNIV,JEWISH GEN HOSP,LADY DAVIS INST MED RES,MONTREAL,PQ H3T 1E2,CANADA
关键词
hepatitis B virus (HBV); hepatitis C virus (HCV); hepatitis; cytochrome P-450s; genotoxicity;
D O I
10.1177/019262339602400408
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Studies were carried out to test the hypothesis that inflammatory liver disease increases the expression of specific cytochrome P-450 isoenzymes involved in aflatoxin B-1 (AFB) activation. The immunohistochemical expression and localization of various human cytochrome P-450 isoforms, including CYP2A6, CYP1A2, CYP3A4, and CYP2B1, were examined in normal human liver and liver with hepatitis and cirrhosis. The constitutive expression of CYP3A4 in normal liver showed a characteristic pattern of distribution in centrilobular hepatocytes, whereas CYP1A2, CYP2A6, and CYP2B1 were expressed uniformly throughout the liver acinus. In sections of liver infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), the expression of CYP2A6 was markedly increased in hepatocytes immediately adjacent to areas of fibrosis and inflammation. CYP3A4 and CYP2B 1 were induced to a lesser degree, and expression of CYP1A2 was unaffected. In HBV-infected liver, double immunostaining revealed that overexpression of CYP2A6 occurred in hepatocytes expressing the HBV core antigen. In HCV-infected liver, CYP2A6, CYP3A4, and CYP2B 1 were overexpressed in hepatocytes with hemosiderin pigmentation. These results suggest that alterations in phenotypic expression of specific P-450 isoenzymes in hepatocytes associated with hepatic inflammation and cirrhosis might increase susceptibility to AFB genotoxicity.
引用
收藏
页码:458 / 467
页数:10
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