Overexpression of cytochrome P-450 isoforms involved in aflatoxin B1 bioactivation in human liver with cirrhosis and hepatitis

Toxicol Pathol. 1996 Jul-Aug;24(4):458-67. doi: 10.1177/019262339602400408.


Studies were carried out to test the hypothesis that inflammatory liver disease increases the expression of specific cytochrome P-450 isoenzymes involved in aflatoxin B1 (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 CYP2B1 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 CYP2B1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aflatoxin B1 / toxicity*
  • Aged
  • Budd-Chiari Syndrome / enzymology
  • Carcinogens / toxicity*
  • Chemical and Drug Induced Liver Injury / enzymology*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Female
  • Hepatitis, Viral, Human / enzymology
  • Hepatitis, Viral, Human / pathology
  • Humans
  • Immunohistochemistry
  • Isoenzymes / biosynthesis*
  • Liver / enzymology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / enzymology*
  • Liver Cirrhosis, Alcoholic / enzymology
  • Male
  • Middle Aged
  • Viral Core Proteins / metabolism


  • Carcinogens
  • Isoenzymes
  • Viral Core Proteins
  • Cytochrome P-450 Enzyme System
  • Aflatoxin B1