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.
Ono-Ogata
Tomoko
T
National Veterinary Assay Laboratory, Tokyo, Japan. tomokot@nval.nval.go.jp
Ogino
Tomoe
T
Nishikawa
Michiko
M
Ohta
Toshihiro
T
Yamagata
Hideo
H
D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000633:toxicity*; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009573:Nitrites / Q000494:pharmacology*; D011319:Primaquine / Q000633:toxicity; D011739:Pyrimethamine / Q000633:toxicity; D011743:Pyrimidines / Q000633:toxicity; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014295:Trimethoprim / Q000633:toxicity
D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D009153:Mutagens; D009573:Nitrites; D011743:Pyrimidines; C033222:diaveridine; C004331:pamaquine; D014295:Trimethoprim; D011319:Primaquine; C016038:pentaquine; D011739:Pyrimethamine