May antioxidants status depletion by Tetradifon induce secondary genotoxicity in female Wistar rats via oxidative stress?

Tetradifon is a potent organochlorine acaricide with an estrogen-like structure. The wide spread use of this chemical is likely to pollute the environment. Only few studies have been reported for the evaluation of its short- and long-term toxic effects including genotoxicity and carcinogenicity and there have been conflicting results in in vitro and in vivo test systems. In this work, we have evaluated Tetradifort for its ability to induce genotoxic damages in female Wistar rats. A single cumulative dose of 2430 mg/kg BW was administrated orally for 12 female rats of 190 g BW during 12 weeks. Twelve additional rats, no treated, have served as control. Animals were sacrificed after 6 and 12 weeks of treatment. Genetic toxicity studies were conducted in rats bone marrow, by chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs) assays. The oxidative stress status of treated animals has been also evaluated by assessment of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS). Some serum parameters: vitamins (A and E), triglyceride (TG) and total antioxiclants status (TAS) were determined. Our results showed a significant increase in tissue TBARS concentrations in the two treated groups suggesting that Tetradifon induce an oxidative stress. Elsewhere, rats treated with Tetradifon exhibited a statistical decrease in serum level of vitamin E and a significant depletion of serum total antioxidant status. Whereas, in comparison to control rats, treated animal cells did not show a significant increase in either the frequency of SCEs or CAs. These results indicate that Tetradifon did not present direct genotoxic effect in female Wistar rats. But we suggest that its inducting of an oxidative stress may lead to indirect mutagenecity that should be evaluated by other series of in vivo genotoxicity assays as micronucleus test or comet assay. (c) 2007 Published by Elsevier Inc.