IMMUNOLOGICAL CROSS-REACTIVITY OF RAT LIVER AND HUMAN CYTOCHROMES P-450

Abstract

Rabbit antibodies raised to phenobarbital–treated rat liver cytochrome P–450 were more effective in inhibiting d –benzphetamine N –demethylase activity in human liver microsomes than were antibodies raised to 3–methylcholanthrene–treated rat liver cytochrome P–450. These antibodies also inhibited benzo(a) pyrene hydroxylation in human liver microsomes, although the inhibition patterns did not follow a general pattern as in the case of benzphetamine demethylase activity. The antibodies raised to 3–methylcholanthrene–treated rat cyto–chromes P–450 were highly effective in inhibiting benzo(a)– pyrene hydroxylase in human monocytes and especially in lymphocytes; antibodies raised to phenobarbital–treated rat P–450 were considerably less effective. Human liver microsomes were more effective in eliciting complement fixation with antibodies raised to phenobarbital– than to 3–methylcholanthrene–treated rat liver cytochrome P–450. Complement fixation in such systems appears to result from similarity of certain rat and human liver cytochrome P–450 antigenic determinants, as fixation could be inhibited by removal of cytochrome P–450–directed antibodies from the total immunoglobulin population and highly–purified human cytochrome P–450 was more effective than liver microsomes in producing fixation. Human liver microsomes prepared from five different individuals all produced ≥ 90% complement fixation, but variations were observed in the fixation curves plotted either versus microsomal protein or versus spectrally–detectable microsomal cytochrome P–450.