Mutagenic evaluation of antiprotozoal drugs as a indicator of their carcinogenicity
2007
Ogata, T.(Japan. Ministry of Agriculture, Forestry and Fisheries, Kokubunji, Tokyo. National Veterinary Assay Lab.)
Many antiprotozoal drugs are used in the field of veterinary medicine. However, some old antiprotozoal veterinary medicines that are still used in Japan have not been evaluated in long-term carcinogenicity tests. It is known that there is a correlation between mutagenicity and carcinogenicity. Therefore, we examined the mutagenic activities of antiprotozoal drugs (four diaminopyrimidine derivatives [pyrimethamine, diaveridine, trimethoprim and ormetoprim] and three 8-aminoquinoline derivatives [primaquine, pentaquine and pamaquine]) to predict their cancer-causing risk. At first, we examined the mutagenic activities of the drugs in the bacterial reverse mutagenicity test and in the chromosome aberration test in cultured Chinese hamster (CHL) cells. Next, we used the alkaline single-cell gel electrophoresis (SCG or Comet) assay and the bone marrow micronucleus test to evaluate in vivo genotoxicity in rats and mice. The results indicate that comprehensive evaluation using a combination of mutagenicity tests is required to evaluate the safety of antiprotozoal drugs.
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