IMMUNOTOXICOLOGY AND EXPRESSION OF HUMAN CYTOCHROME-P450 IN MICROORGANISMS

Drug-induced hepatitis can be caused by an abnormal immunological resp onse. In the case of tienilic acid- and dihydralazine-induced hepatiti s, we postulated a scheme in which a P450 produced a reactive metaboli te (step 1); this reactive metabolite bound to the P450 producing it ( step 2) leading to a neoantigen triggering the immune response (step 3 ); the autoantibodies produced during the immune response recognized t he P450 producing the reactive metabolite (step 4). The use of microor ganisims (yeast or bacteria) expressing cloned human P450 helped in pr oving some steps of this postulated scheme, particularly steps 1 and 4 .