Rat의 3-methylcholanthrene에 의한 Flavin-containing Monooxygenase (FMO1) 효소의 유도

초록

Flavin-containin monooxygenase (FMO) known not to be induced by xenobiotics has been induced with a polycyclic aromatic hydrocarbon, 3-metylcholanthrene (3MC). Liver tissues were used to study the inductive effect of 3MC on FMO1 isoform which is the major form present in rat liver. The hepatic FMo1 was prominantly increased both at transcription and translation levels by pretreatment of rats with 3MC. Evidences for significant induction of rat FMO1 were observed not only in the mRNA production (4.5 fold) identified from RT-PCR results, but also in the catalytic activity of the enzyme (2.9 fold) which has been measured by thiobenzamide S-oxidation assay using the induced rat liver microsomes. Our finding is the first report showing that hepatic FMO1 is inducible with a polycyclic aromatic hydrocarbon compound. As the FMO plays crucial roles in the oxidation of N- and S-containing drugs, if the FMO is also inducible with other environmental polycyclic aromatic hydrocarbon compounds in general, this finding will have important consequences in understanding the altered half-lives of many clinically useful drugs.