Mutagenesis Advance Access published online on August 8, 2006
Mutagenesis, doi:10.1093/mutage/gel036
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Unité des Cyanobactéries, Institut Pasteur, 28, Rue du Dr Roux, 75724 Paris Cedex15, France
* To whom correspondence should be addressed. Nitrofurans are widely used in human medicine, as nitrofurantoin and nifuroxazide, still prescribed for long-term antimicrobial prophylaxis of urinary tract and gastrointestinal infection in humans respectively. Recent experiments in mammals, as well as reports mentioning toxic effects in humans associated with a long-term use, specially in the case of nitrofurantoin, raised the need for reevaluating their genotoxicity. The objective of this study was to determine whether these two compounds induce a mutagenic effect in the Big Blue transgenic mouse mutation assay. Mice were orally treated either with nitrofurantoin or nifuroxazide for five consecutive days and sacrificed 3 weeks later. In order to optimize the genotoxic response, the doses used for each compound were 25-fold higher as the posology in humans. They corresponded to 50% of the highest doses tolerated by mice. The mutant frequency was determined from kidney, lung, bladder, caecum, colon, small intestine, spleen and stomach. A weak mutagenic response of nitrofurantoin-treated mice specifically in the kidney was observed. As in the case of other nitrofuran compounds, the mutation spectra determined from treated samples exhibited slightly more GC
Received May 18, 2006
Revised July 7, 2006
Accepted July 9, 2006
Original article
Organ-targeted mutagenicity of nitrofurantoin in Big Blue transgenic mice
Philippe Quillardet 1, Xavier Arrault 2, Valérie Michel 3, and Eliette Touati 3 *
2 Service de Pharmacie Clinique et des Biomatériaux, Groupe Hospitalier Bichat-Claude Bernard, AP-HP, 46, Rue Henri Huchard, 75877 PARIS Cedex 18, France
3 Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 28, Rue du Dr Roux, 75724 Paris Cedex15, France
Eliette Touati, E-mail: etouati{at}pasteur.fr
Abstract 
TA transversions as compared with untreated conditions. These data are relevant to the targeted action of nitrofurantoin as a urinary antimicrobial agent. No significant increase of mutants was detected in the case of nifuroxazide-treated mice whatever the organs analysed.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Murphey, Y. Yamazaki, C. A. McMahan, C. A. Walter, R. Yanagimachi, and J. R. McCarrey Epigenetic regulation of genetic integrity is reprogrammed during cloning PNAS, March 24, 2009; 106(12): 4731 - 4735. [Abstract] [Full Text] [PDF]
|
|