A high level of Cyp2a-5 was found in spontaneous and transplanted mouse hepatomas compared with normal liver. Increased expression of Cyp2a-5 was associated with an increase in coumarin 7-hydroxylation, a marker activity of Cyp2a-5, and the corresponding mRNA, suggesting that regulation of Cyp2a-5 in hepatomas is pretranslational. In contrast, the total P450 content and arylhydrocarbon hydroxylase and amidopyrene demethylase activities decreased. Pyrazole, a strong inducer of Cyp2a-5 in normal mouse livers, also increases this isozyme in hepatomas. A parallel increase in the corresponding mRNA suggests that pyrazole, like the formation of hepatomas, affects the regulation of Cyp2a-5 pretranslationally.

1. Rat hepatoma 27 after intrahepatic transplantation shows a low but detectable level of cytochrome P450 and P450-dependent activities. The same hepatoma transplanted intramuscularly does not show a detectable amount of cytochrome P450 and P450-dependent activities. 2. Different types of cytochrome P4501A inducers were able to induce 1A isoforms in the intrahepatic hepatoma 27 transplants but not in the intramuscular transplants. 3. Immunohistochemical analysis demonstrates that not all cells in hepatoma 27 transplanted into the liver could be induced with 1A-inducer. The cells of the adenomatous structures of hepatoma 27 are not reactive with 1A antibodies.

No abstract