The alteration of hepatic cytochrome P-450 subpopulations of phenobarbital-induced and uninduced rat by regioselective hepatotoxins.

Two centrilobular hepatotoxins, bromobenzene and acetaminophen, and a periportal hepatotoxin, allyl alcohol, caused necrosis and cytochrome P-450 depletion in the livers of uninduced and phenobarbital-induced rats. The per cent loss of cytochrome P-450 and its enzymatic activity exceeded the amount of hepatic necrosis evident by light microscopy, indicating limitations to the use of regioselective hepatotoxins as probes for the intralobular localization of cytochrome P-450 functions. No hepatotoxin was specific for a single cytochrome P-450 subpopulation as defined either by DEAE-cellulose fractionation or by the ability to form metabolic intermediate complexes from two classes of substrates, but some selectivity was apparent. The susceptibilities of subpopulations as defined by DEAE fractionation to hepatotoxin-linked depletion differed in phenobarbital-induced and uninduced rats.