IMMUNOHISTOCHEMICAL PROPERTIES OF DIPYRONE-INDUCED CYTOCHROMES P450 IN RATS

1 Rat hepatic cytochrome P450s induced by dipyrone were studied enzyma tically, immunochemically and immunohistochemically. 2 Dipyrone admini stered to male Wistar rats increased pentoxyresorufin O-depentylation (PROD), ethoxyresorufin O-deethylation (EROD) and 7-ethoxycoumarin O-d eethylation (ECOD) activities up to 44-, 1.9-, and 2.6-fold, respectiv ely. Aryl hydrocarbon hydroxylase (AHH) activity was not affected. 3 I mmunoinhibition with the monoclonal antibody (Mab) 2-66-3 (to CYP2B1/2 ) markedly decreased PROD and EROD activities, but not AHH activity. T he Mab 1-7-1 (to CYP1A1/2) was without effect. 4 Histochemically, the Mab 2-66-3 gave a strong and uniform staining in livers from dipyrone- treated rats, whereas the Mab 1-7-1 gave a positive reaction in a narr ow perivenous strip. 5 The induction pattern as well as inhibition by the Mabs convincingly demonstrate the predominant production of CYP2B1 /2 in the induction spectrum of dipyrone. The increase in enzyme activ ities other than PROD may be due to the overlapping substrate specific ity of CYP2B1/2 enzymes. The immunohistochemical analysis also indicat ed the participation of CYP1A1/2.