MUTAGENIC EVALUATION OF PRANOPROFEN, A NEW ANTI-INFLAMMATORY AGENT

The mutagenicity of pranoprofen, a new antiinflammatory agent primarily used in Japan, was evaluated by employing several different methods such as the Ames test, micronucleus test, and the sister chromatid exchange test. For the Ames test, various doses of pranoprofen (5 and 1 mg, 100, 10, and 1 ${\mu}$g per plate) were applied, with or without the mammalian liver S-9 fraction, to the S. typhimurium LT2. For the micronucleus test, 24 hours after administering the various doses of pranoprofen (200, 100, and 50 mg/kg) to male mice by aral intubation, the femura of each group were isolated and the bone marrow samples were prepared. The micronucleated red cells and the ratio of the polychromatic versus the normochroomatic cells were counted. For the sister chromatid exchange test, the maximal non-cytotoxic concentrations (10 to 0.1 mM pranoprofen) were applied to the culture media of the Chinese Hamster Ovary (CHO) cells for 24 hrs. The numbers of revertant colonies did not increase with the increasing doses of pranoprofen when teseted with various strains of S. typhimurium. In the micronucleus test employing mice, the pranoprofen was identkfied to be a non-clastogen and a non-spindle poison. In the sister chromatid exchange test employing the cultured CHO cells, the pranoprofen did not increase the incidences of chromosomal abnormality. Based on these results, pranoprofen was found to have no mutagenic activity.