Daidzein modulates induction of hepatic CYP1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene in mice.
We investigated the hepatic effects of daidzein on the 7,12-dimethylbenz(a)anthracene (DMBA)-induced enzymatic activity and expression of CYP1A1 and CYP1B1 in mice. Daidzein was administered orally to mice at 5 or 25 mg/kg BW for three weeks, after which DMBA (34 mg/kg BW) was administered intragastrically twice a week for two weeks. Twenty-four hours after the last DMBA treatment, the mice were sacrificed. DMBA induced CYP1 activity as well as the expression of CYP1A1 and CYP1B1. The catalytic activity of CYP1 enzymes was determined as 7-ethoxyresorufin-O-deethylase (EROD) activity. Each of these effects was significantly reduced by daidzein; however, the reduction was more pronounced for CYP1A1. Daidzein also exerted a negative effect on the transcription of CYP1A1 by AhR, similar to its effect on CYP1A1. The AhR-dependent inhibition of CYP1 by daidzein may explain the anticancer effects of daidzein.
Choi
Eun Jeong
EJ
Plant Resources Research Institute, Duksung Women's University, Seoul, 132-714, Korea. ejchoi@duksung.ac.kr
Kim
Taehee
T
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D015151:Immunoblotting; D007529:Isoflavones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007529:Isoflavones; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D015127:9,10-Dimethyl-1,2-benzanthracene; C004742:daidzein; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1