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Environmental and molecular mutagenesis

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


PMID 11813295

Abstract

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.

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