Mutagenicity of urine from mice exposed orally to nitrite and various aminated antiparasitic drugs.
Mutagenic N-nitroso compound formation from the in vitro reaction of amebicides and anthelmintic drugs, which are pyrimidine derivatives or contain secondary aliphatic amines or heterocyclic nitrogens, has been previously described (Arriaga Alba et al.: Environmental and Molecular Mutagenesis 12:65-73, 1988). Under similar conditions, antiparasitic drugs containing halogenated derivatives of tertiary amines or quaternary ammonium salts do not form mutagenic nitrosated compounds. In the present study the mutagenic activity of mouse urine was determined after oral administration of sodium nitrite and the two above-mentioned groups of drugs (pyrantel pamoate, chloroquine, piperazine and dehydroemetine/iodochlorhydroxyquin and bephenium hydroxynaphthoate, respectively). Results show that the simultaneous administration of piperazine or chloroquine with sodium nitrite produced urinary mutagens that appeared conjugated as glucuronides, whereas pyrantel pamoate and dehydroemetine in the presence of nitrite caused only slightly mutagenic urine. No mutagenic activity was detected in the urine of mice to which halogenated derivatives of tertiary amines (iodochlorhydroxyquin) or quaternary ammonium salts (bephenium hydroxynaphthoate) were administered together with nitrite.
Arriaga Alba
M
M
Instituto de Investigaciones Biomédicas, U.N.A.M., México, D.F.
Espinosa Aguirre
J
J
Ramírez
J
J
Cortinas de Nava
C
C
D000563:Amebicides / Q000378:metabolism*; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D002738:Chloroquine / Q000378:metabolism; D008297:Male; D051379:Mice; D009153:Mutagens / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D000077489:Piperazine; D010879:Piperazines / Q000378:metabolism; D012977:Sodium Nitrite / Q000378:metabolism*; D014556:Urine / Q000032:analysis
D000563:Amebicides; D000871:Anthelmintics; D009153:Mutagens; D009573:Nitrites; D010879:Piperazines; D000077489:Piperazine; D002738:Chloroquine; D012977:Sodium Nitrite