Atovaquone, a hydroxynaphthoquinone, is an anti-parasite
drug, selectively targeting the mitochondrial respiratory chain of
malaria parasite. It is used for both the treatment and prevention of
malaria, usually in a fixed combination with
proguanil. Although
atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of
atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of
malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that
atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that
atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that
atovaquone is safe from the aspect of genototoxicity in the recommended dosages.