Assessment of the genotoxicity and antigenotoxicity of (+)-usnic acid in V79 cells and Swiss mice by the micronucleus and comet assays

Usnic acid is one of the most common and abundant metabolites found in various lichen genera, which are important sources of biologically active compounds. The aim of this study was to evaluate the genotoxic and antigenotoxic potential of (+)-usnic acid (UA) by the micronucleus and comet assays in V79 cell cultures and Swiss mice. For assessment of genotoxicity, V79 cells were treated with 15, 30, 60, and 120μg/mL UA, established based on clonogenic efficiency cytotoxic assay. Swiss mice were treated with UA doses of 25, 50, 100, and 200mg/kg body weight. The same concentrations of UA were combined with methyl methanesulfonate (MMS) for evaluation of antigenotoxicity. The in vitro results demonstrated that UA induced DNA damage at concentrations of 60 and 120μg/mL in the comet assay. However, no genotoxic effect was observed in the micronucleus test using V79 cells at the concentrations tested. No genotoxic effects were observed for the different UA treatments in in vivo test system. Combined administration of UA and MMS significantly reduced the frequencies of micronuclei and DNA damage in vitro and in vivo when compared to treatment with MMS alone. Although the mechanisms underlying the protective effect of UA are not completely understood, the antioxidant activity of this metabolite may explain its protective effect against MMS-induced genotoxicity.