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-metabolizing enzymes were determined with either catalytic assays or by quantifying levels of total cellular RNA coding for the individual genes of interest. The high dose of DAS induced the cytochrome P450 (CYP) 2B subfamily to near maximal levels [i.e. similar to those induced by phenobarbital (PB)] and induced the CYP3A subfamily, while having minimal effects on the levels of the CYP1A subfamily. In addition, DAS induced the glutathione S-transferase alpha subfamily, the glutathione S-transferase 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. Finally, we determined that DAS induced the levels of a specific nuclear binding protein that appears to be associated with the induction of various genes that are part of the pleiotropic response caused by PB-type inducers.
Dragnev
K H
KH
Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA.
Nims
R W
RW
Lubet
R A
RA
D000498:Allyl Compounds; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D003634:DDT / Q000494:pharmacology; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000494:pharmacology*; D014158:Transcription, Genetic
D000498:Allyl Compounds; D000975:Antioxidants; D065607:Cytochrome P-450 Enzyme Inhibitors; D013440:Sulfides; C038491:allyl sulfide; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; D005982:Glutathione Transferase; D010634:Phenobarbital