Modulation of mutagenesis, DNA binding, and metabolism of aflatoxin B₁ 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 [³H]AFB₁ binding to calf thymus DNA were assessed. Organosoluble and water-soluble metabolites of [³H]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.