Previous work in our laboratory demonstrated that
cytochrome P450 2B1 in rat liver was induced, but P450 2E1 was inhibited and inactivated, by
diallyl sulfide (
DAS), a compound derived from garlic. Such a selective effect on
P450 enzymes is of considerable interest toward the understanding of dietary effects on
xenobiotic metabolism. In the present study, the mechanism of P450 2B1 induction by
DAS was investigated. Following a single dose of
DAS (200 mg/kg
body weight, ig), liver microsomal
pentoxyresorufin dealkylase (PORd) activity, a representative activity of P450 2B1, was induced 3-, 16-, 26-, and 43-fold at 6, 12, 18, and 24 h after the treatment, respectively. A corresponding increase in the level of P450 2B1/2
protein was observed by immunoblot analysis. The level of P450 2B1/2
mRNA in rat liver also increased markedly, reaching a maximum at 12 h after the
DAS treatment. Hybridization with the
isozyme-specific
oligonucleotide probes revealed that the
mRNA levels of both P450s 2B1 and 2B2 were induced. In contrast, the level of P450 2E1
mRNA in the liver of
DAS-treated rats was not changed. The results of nuclear run-on assay revealed that the transcriptional rate of P450 2B1/2 genes in the rat liver increased 13-fold at 6 h after
DAS administration and returned to the control value at 24 h. The transcription of P450 2B1/2 genes was blocked completely by
alpha-amanitin, an inhibitor of
RNA polymerase II. These results clearly demonstrate that the induction of P450 2B1/2 in rat liver by
DAS is mainly due to transcriptional activation. In the
DAS-treated rats, P450 2B1/2
mRNA was also markedly induced in the stomach and duodenum. The maximal induction was found at 12 h after the treatment while the levels of P450 2B1/2
mRNA increased 66-fold in the duodenum and 23-fold in the stomach.
DAS treatment, however, did not change the levels of P450 2B1/2
mRNA in the lung and nasal mucosa.