Induction of flavin-containing monooxygenase (FMO1) by a polycyclic aromatic hydrocarbon, 3-methylcholanthrene, in rat liver.
Flavin-containing monooxygenase (FMO), known not to be induced by xenobiotics, has been induced by a polycyclic aromatic hydrocarbon, 3-methylcholanthrene (3MC). We have found a prominent augmentation of hepatic FMO1 both at transcription and translation levels by pretreatment of rats with 3MC. Liver tissues were used to study the inductive effect of 3MC on the FMO1 isoform, the major form present in rat liver. Evidence for significant induction of rat FMO1 was observed in mRNA production (3.5 fold) identified from reverse transcription-polymerase chain reaction (RT-PCR) results. Induction was also seen in the catalytic activity of the enzyme (2.9 fold) as measured by the thiobenzamide S-oxidation assay using induced rat liver microsomes. Our finding is the first report to indicate that hepatic FMO1 can be induced with a polycyclic aromatic hydrocarbon compound. FMO plays crucial roles in the oxidation of N- and S-containing drugs. If FMO is also inducible with other environmental polyaromatic hydrocarbon compounds in general, this finding will have important consequences in understanding the altered half-lives of many clinically useful drugs.
Chung
W G
WG
Department of Pharmacology and Toxicology, College of Medicine, Inha University, Inchon, Korea.
Park
C S
CS
Roh
H K
HK
Cha
Y N
YN
D000818:Animals; D001483:Base Sequence; D004790:Enzyme Induction / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000502:physiology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013854:Thioamides / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology
D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D013854:Thioamides; D015262:Xenobiotics; D008748:Methylcholanthrene; C015539:thiobenzamide; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)