ALTERED EXPRESSION OF HEPATIC CYP1A ENZYMES IN RAT HEPATOCARCINOGENESIS

Hyperplastic nodules of the liver were induced by treating male F344 r ats with a combination of diethylnitrosamine and partial hepatectomy. The livers were examined for the expression of cytochrome P450 (CYP) e nzymes, mainly CYP1A1 and CYP1A2; the amount and activity of the enzym es in the microsomes were assessed by enzymatic and immunological meth ods. Levels of CYP1A mRNAs were assayed by Northern blotting. In the l iver bearing hyperplastic nodules, the total amount of microsomal CYP enzymes decreased to about 50% of the control. The microsomal activiti es for the CYP1A2-mediated activation of carcinogenic heterocyclic ami nes decreased to about 20% of the corresponding controls, in associati on with decreases in the levels of mRNA and protein of CYP1A2. Further more, the inducibility of CYP1A2 by CYP1A inducers such as 3-methoxy-4 -aminoazobenzene and 3-methylcholanthrene was also decreased at the mR NA, protein and activity levels. On the other hand, CYP1A1 enzyme, whi ch was undetectable in control rat liver, appeared in the liver bearin g hyperplastic nodules, but its inducibility by a CYP1A inducer decrea sed slightly. The present findings indicated that individual CYP1A enz ymes are differently regulated, and the expression of CYP1A2 is reduce d preferentially in the liver bearing hyperplastic nodules.