title: Rat hepatic CYP1A1 and CYP1A2 induction by menadione.
abstract: The effects of menadione on activities and expression of cytochrome P450 (CYP) 1A subfamily (CYP1A) isozymes in rat hepatic tissue were examined. When rats were treated orally with 15 mg/kg menadione for 4 days, the elevation of hepatic CYP1A1/1A2 specific activities in microsomal preparations was detected with approximately 5.4- and 2.5-fold increase over control values for ethoxyresorufin-O-deethylase (EROD, CYP1A1) and methoxyresorufin-O-demethylase (MROD, CYP1A2) activities, respectively. CYP1A1 and CYP1A2 mRNA levels in the liver of menadione-treated rats were approximately 11.8- and 1.8-fold higher than in controls, respectively, whereas the expression of the CYP1A regulatory proteins aryl hydrocarbon-receptor (AhR) and AhR nuclear translocator (Arnt) was not changed at the mRNA level. The result of this study demonstrates that menadione induces CYP1A1/1A2 expression in vivo through either transcriptional activation and/or mRNA stabilization.
authors.affiliation: Institute of Molecular Biology and Biophysics, Siberian Division of Russian Academy of Medical Sciences, Timakova str. 2, Novosibirsk 630090, Russia. ysidorova@soramn.ru
authors.forename: Y A
authors.initials: YA
authors.lastname: Sidorova
authors.forename: A Y
authors.initials: AY
authors.lastname: Grishanova
authors.forename: V V
authors.initials: VV
authors.lastname: Lyakhovich
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000284:Administration, Oral; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis; D024483:Vitamin K 3 / Q000633:toxicity*
chemical_list: C497398:ARNT protein, rat; D000199:Actins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D024483:Vitamin K 3; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2