Expression of cytochrome P450 1A1/2 and 3A4 in liver tissues of hepatocellular carcinoma cases and controls from Taiwan and their relationship to hepatitis B virus and aflatoxin B-1- and 4-aminobiphenyl-DNA adducts

Cytochrome P450 enzymes play a major role in the metabolism of several of t he chemical carcinogens involved in the development of hepatocellular carci noma (HCC). To investigate by immunohistochemistry interindividual differen ces in these enzymes, polyclonal antisera and immunoperoxidase staining wer e used to detect the expression of CYP1A1/2 and 3A4 in 37 surgical control tissues and 105 tumour and adjacent non-tumour tissues of HCC cases from Ta iwan. There was variability in the expression and staining pattern for both CYP1A1/2 and 3A4 in all tissue types. In tissues from controls, there was no correlation between P450 expression and smoking history or hepatitis B v irus antigen status. Since these samples had been previously analysed for t he DNA adducts of aflatoxin B-1 (AFB(1)), a dietary mould contaminant, and 4-aminobiphenyl (4-ABP), a component of cigarette smoke, we also investigat ed the relationship between P450 levels and DNA adducts. 4-ABP-DNA adducts were higher in tissues with elevated levels of CYP1A1/2 (p = 0.02). Overall there was no relationship between CYP1A1/2 or CYP3A4 and AFB(1)-DNA adduct s in control tissues. Staining intensity for CYP1A1/2 and 3A4 followed the order: tumour tissues <control tissues <adjacent non-tumour tissues. CYP1A1 /2 levels tended to be lower in tumour and adjacent non-tumour tissues than for CYP3A4. In HCC cases, 4-ABP-DNA adducts were higher in subjects with h igher levels of CYP1A1/2, stratified by tissue type, but these differences were not significant. For CYP3A4, in contrast to control tissues, there was a significant association with AFB(1)-DNA adducts in tumour and adjacent n on-tumour tissue of HCC cases. These results suggest that one factor influe ncing carcinogen-DNA adducts is levels of specific P450 enzymes. However, a dduct formation in vivo is a complex processes dependent upon numerous gene tic and environmental factors.