Mutagenic activity and mutational specificity of antiprotozoal drugs with and without nitrite treatment.

We examined the mutagenic activities of six antiprotozoal drugs (three diaminopyrimidine compounds [pyrimethamine, diaveridine, and trimethoprim] and three 8-aminoquinoline derivatives [primaquine, pentaquine, and pamaquine]) in Escherichia coli WP2uvrA/pKM101 and Salmonella typhimurium TA100 and TA98 with and without nitrite treatment. The diaminopyrimidine compounds showed no mutagenic activity under any condition in any strain. The 8-aminoquinoline derivatives after nitrite treatment at 5-20 mM for 5 min at pH 3, on the contrary, showed clear mutagenicity in TA100 and WP2uvrA/pKM101 in the presence and absence of S9 mix. We concluded that 8-aminoquinoline derivatives became mutagenic following nitrite treatment. In the Lac(+) reversion assay with E. coli WP3101P-WP3106P, these nitrite-treated compounds induced G:C --> A:T transitions and G:C --> T:A transversions in the absence of S9 mix. On the other hand, A:T --> T:A transversions were induced only in the presence of S9 mix, suggesting a different kind of products may be responsible for the mutagenicity.