[Effect of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo (a) pyrene].
Glycyrrhetinic acid (GA) is an active component of Glycyrrhiza uralensis Fisch. In this study, the effects of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo (alpha) pyrene were studied. Mouse ear edema was visible obviously at the 6th h after topical application of single dose croton oil. A topical application of croton oil on the back of ICR mice for 5 h, induced elevation of ornithine decarboxylase (ODC) activity in epidermal. The administration of glycyrrhetinic 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 (alpha) pyrene obviously caused DNA damage and unscheduled DNA synthesis mediated by S9 fraction in Chinese hamster lung cell line. Glycyrrhetinic acid was found to protect the rapid DNA damage induced by benzo (alpha) pyrene. At concentration of 5 micrograms.ml-1, glycyrrhetinic acid exhibited 70% protection. At 20 micrograms.ml-1, this action was more potent and approached to 80%. The addition of hydroxyurea 10 mmol.L-1 suppressed DNA replicative synthesis to 84.04% and benzo (alpha) pyrene stimulated the DNA repair synthesis (6-fold). Glycyrrhetinic acid (20 micrograms.ml-1 and 50 micrograms.ml-1 significantly decreased the stimulation of DNA repair synthesis induced by benzo (alpha) pyrene. This suggests that glycyrrhetinic acid has effective anti-initiating and anti-promoting activities and could be used for cancer chemopreventive purpose.
Chen
X G
XG
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
Han
R
R
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology; D001564:Benzo(a)pyrene; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D001564:Benzo(a)pyrene; D004247:DNA; D006034:Glycyrrhetinic Acid