THE CHEMOPREVENTIVE AGENT DIALLYL, SULFIDE - A STRUCTURALLY ATYPICAL PHENOBARBITAL-TYPE INDUCER

Diallyl sulfide (DAS), a known chemopreventive agent, was administered i.g. (200 or 500 mg/kg body wt/day) to male F344/NCr rats for 4 days. Livers were removed, and hepatic levels of a variety of drug-metaboli zing enzymes were determined with either catalytic assays or by quanti fying levels of total cellular RNA coding for the individual genes of interest The high dose of DAS induced the cytochrome P450 (CYP) 2B sub family to near maximal levels [i.e. similar to those induced by phenob arbital (PB)] and induced the CYP3A subfamily, while having minimal ef fects on the levels of the CYP1A subfamily. In addition, DAS induced t he glutathione 5-transferase alpha subfamily, the glutathione S-transf erase mu subfamily, and epoxide hydrolase. Unlike PB, however, DAS was also able to induce quinone oxidoreductase. In fact, the pleiotropic hepatic response to DAS appeared to be similar to that elicited by PB, with the exception that only DAS induced quinone oxidoreductase. Fina lly, we determined that DAS induced the levels of a specific nuclear b inding protein that appears to be associated with the induction of var ious genes that are part of the pleiotropic response caused by PB-type inducers.