SIMILARITY OF NUCLEAR AND MICROSOMAL CYTOCHROMES-P-450 IN THE INVITRO ACTIVATION OF AFLATOXIN-B-1

The metabolism of the hepatocarcinogen aflatoxin B1 (AFB1) by rat liver nuclear and microsomal preparations was examined using covalent binding of AFB1 to nucleic acids as an index of activation. Nuclear activation of AFB1 was induced by treatment of rats with either phenobarbital or 3-methylcholanthrene. The nuclear enzymes catalyzed AFB1 binding to endogenous nucleic acids (principally DNA) but the binding was considerably enhanced over a wide concentration range of AFB1 (2-500 μM) by the addition of microsomal enzymes. Antibodies, prepared to microsomal cytochromes P-450, inhibited metabolism of both AFB1 and the model substrate 7-ethoxycoumarin in microsomal and nuclear preparations; antigen-antibody specificity was observed with regard to induction of the animals used for preparation of the enzymes. Immunodiffusion studies also indicated that microsomal and nuclear cytochromes P-450 are similar. The AFB1-dna adducts produced by nuclei and microsomes were identical as judged by high pressure liquid chromatography of hydrolysates. © 1979.