Nitrofurazone--genotoxicity studies in mammalian cells in vitro and in vivo.
Nitrofurazone has been examined for genetic effects in mammalian cells in vitro and in vivo. In the in vitro studies in Chinese hamster ovary (CHO) cells, metaphase analysis was carried out at different sampling times after nitrofurazone treatment and gene mutation leading to hypoxanthine-guanine phosphoribosyltransferase deficiency was also investigated. Both assays were carried out in the presence and absence of a metabolic activation system (S-9 mix). Metaphase analysis was also carried out on bone-marrow cells at various sampling times after treatment of rats with a single oral dose of nitrofurazone and at one sampling time after administration of five daily oral doses. In the in vitro studies a dose-related increase in aberrant metaphases was observed after nitrofurazone treatment both with and without metabolic activation, but the gene mutation assay was negative. In vivo, despite the use of high doses of nitrofurazone (up to 400 mg/kg body weight) resulting in evidence of toxicity and a reduction in the mitotic index of bone-marrow cells, there was no evidence that nitrofurazone increased chromosomal damage. It is concluded that although the compound has the capacity to cause chromosomal damage in mammalian cells in vitro, it is detoxified by the metabolic system of the animal. These results, together with existing in vivo data, do not suggest that nitrofurazone is likely to give rise to any genotoxic hazard for man.
D000818:Animals; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008677:Metaphase / Q000187:drug effects; D008940:Mitotic Index / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens; D009583:Nitrofurazone / Q000378:metabolism / Q000633:toxicity*; D010053:Ovary; D051381:Rats; D011919:Rats, Inbred Strains
D009153:Mutagens; D007041:Hypoxanthine Phosphoribosyltransferase; D009583:Nitrofurazone