Inhibitory effect of geniposide on aflatoxin B1-induced DNA repair synthesis in primary cultured rat hepatocytes.
We have previously demonstrated that geniposide (GP) inhibits the aflatoxin B1 (AFB1) induced-hepatotoxicity and hepatic DNA binding in rats. To address the mechanism of action, the effects of GP on AFB1-induced DNA repair synthesis and AFB1 biotransformation in cultured rat hepatocytes were investigated. By evaluation of unscheduled DNA synthesis (UDS), GP reduced AFB1-induced DNA repair synthesis in a dose-dependent manner in hepatocyte cultures. GP elevates the metabolism of AFB1 and decreases the formation of AFM1. The enzyme activities of glutathione S-transferase (GST) and GSH-peroxidase (GSH-Px) in AFB1-treated hepatocyte cultures are enhanced in the presence of GP. GP reduces AFB1-induced DNA repair synthesis through an increased AFB1 detoxication metabolism. It provides one possible mechanism for the chemopreventive activity of GP.
Wang
S W
SW
Institute of Medicine, Chung-Shan Medical and Dental College, Taichung, Taiwan, ROC.
Lai
C Y
CY
Wang
C J
CJ
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D039823:Iridoids; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D039823:Iridoids; D011714:Pyrans; C007835:geniposide; D016604:Aflatoxin B1