Mutagenic effects of niridazole in animal-mediated and in liquid suspension assays using Escherichia coli K-12 as an indicator.
The mutagenic effects of the antischistosomal drug niridazole (1-(5-nitro-2-thiazolyl)-2-imidazolidinone) were investigated in liquid suspension and intrasanguineous animal-mediated assays with mice. As indicator strains Escherichia coli K-12 343/113 (Nir(S)) and a newly constructed niridazole nitroreductase-deficient derivative (Escherichia coli K-12 343/113 Nir(r) 200) were used. With the parental strain (Nir(S)) induction of nalidixic acid- and valine-resistant mutants was observed under in vivo conditions in the liver and, to a lesser extent, in the spleen. Positive results were also found when intestinal homogenates, blood sera, and urine samples of niridazole-treated animals were tested in vitro with the wild-type strain. With Escherichia coli K-12 343/113 Nir(r) 200 no clear-cut positive results were obtained in animal-mediated assays. In liquid suspension assays positive results were restricted to the urine samples. These findings indicate that the positive results obtained with the wild-type strain are due to nitroreduction and that the concentrations of mutagenic metabolites formed by activation processes in the living animal are too low to enable their detection in inner organs, intestines, and the blood with the reductase-deficient strain. In agreement with our present findings showing increased genotoxicity in urine, niridazole causes tumors in rodents preferentially in the kidneys and in the bladder.
Knasmüller
S
S
Institut für Tumorbiologie-Krebsforschung, Universität Wien, Austria.
Szakmary
A
A
D000818:Animals; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009560:Niridazole / Q000378:metabolism / Q000633:toxicity*; D010084:Oxidation-Reduction
D009560:Niridazole