EFFECT OF GLYCYRRHETINIC ACID ON DHA DAMAGE AND UNSCHEDULED DNA SYNTHESIS INDUCED BY BENZO(α) PYRENE

Glycyrrhetinic acid(GA)is an active component of Glycyrrhiza uralensis Fisch.Inthis study,the effects of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis inducedby benzo(α)pyrene were studied.Mouse ear edema was visible obviously at the 6th h after topicalapplication of single dose croton oil.A opical application of croton oil on the back of ICR mice for 5h,induced elevation of ornithine decarboxylase(ODC)activity in epidermal.The administration ofglycyrrhetinic acid(50～200 mg·kg^-1·d^-1)to animals for 3 days exhibited 20%～80%inhibition of epidermal ornithine decarboxylase activity in a dose-dependent manner.Benzo(α)pyreneobviously caused DNA damage and unscheduled DNA synthesis mediated by S₉ fraction in Chinesehamster lung cell line.Glycyrrhetinic acid was found to protect the rapid DNA damage induced bybenzo(α)pyrene.At concentration of 5μg· mL^-1,glycyrrhetinic acid exhibited 70% protection.At20μg·mL^-1 ,this action was more potent and approached to 80%.The addition of hydroxyurea 10mmol·L^-1 suppressed DNA replicative synthesis to 84.4%and benzo(α)pyrene stimulated theDNA repair synthesis(6-fold).Glycyrrhetinic acid(20μg· mL^-1 and 50μg·mL^-1 significantlydecreased the stimulation of DNA repair synthesis induced by benzo(α)pyrene.This suggests thatglycyrrhetinic acid has effective　anti-initiating and ant-promoting activities and could be used forcancer chemopreventive purpose.