MODULATION OF MUTAGENESIS, DNA-BINDING, AND METABOLISM OF AFLATOXIN-B(1) BY LICORICE COMPOUNDS

Three licorice compounds (extract 348, carbenoxolone, and glycyrrhetinic acid) were studied for their effects on aflatoxin B1 (AFB1)-induced mutagenesis using Salmonella typhimurium TA-100 as the bacterial tester strain, and rat liver 9,000 x g supernatant (S-9) as the metabolic activation system. The effects of these compounds on [H-3]AFB1 binding to calf thymus DNA were assessed. Organosoluble and water-soluble metabolites of [H-3]AFB1 were extracted and analyzed by reverse-phase high performance liquid chromatography and alumina column liquid chromatography. All three compounds exhibited a concentration-dependent inhibition of S-9-mediated mutagenesis induced by AFB1. These compounds also significantly inhibited AFB1 binding to DNA and significantly decreased the activation of AFB1 to mutagenic/carcinogenic metabolites. The findings indicate that licorice compounds used in this study possess antimutagenic and, potentially, cancer chemopreventive properties.