Elsevier

Toxicology

Volume 203, Issues 1–3, 15 October 2004, Pages 17-26
Toxicology

Lymphocyte DNA damage in rats exposed to pyrethroids: effect of supplementation with Vitamins E and C

https://doi.org/10.1016/j.tox.2004.05.012Get rights and content

Abstract

Pesticides have been considered potential chemical mutagens. In fact, some studies show that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Experimental evidence shows a marked correlation between mutagenicity and carcinogenicity and indicates that short-term mutagenicity tests are useful for predicting carcinogenicity. The present study on rat exposed to two pyrethroids, cypermethrin and permethrin, showed different lymphocyte DNA damage depending on the type of pyrethroid, the dose, and the period of treatment. Data obtained from comet assay showed that oral treatment with 150 mg/kg body weight/day of permethrin (corresponding to 1/10 of LD50) for 60 days, induced a significant increase in all comet parameters. No lymphocyte DNA damage was measured after treatment with 25 mg/kg body weight/day of cypermethrin (corresponding to 1/10 of LD50) for the same period. A higher dose of permethrin (300 mg/kg body weight/day), for a shorter period (22 days), did not induce lymphocyte DNA damage, while supplementation with 200 mg/kg of Vitamins E and C protected erythrocytes against plasma membrane lipids peroxidation. Moreover, treatment with Vitamins E and C maintained the activity of glutathione peroxidase, which was reduced in the presence of permethrin, and reduced the osmotic fragility, which had increased following permethrin treatment.

Introduction

With the recognition of molecular models of multi-stage carcinogenesis, it was clear that the induction of malignancies is much more complicated than originally thought, involving a series of genetic and epigenetic changes. Both the classical and molecular models, that have been used to describe the process of carcinogenesis, indicate that at least one, and possibly several, mutagenic events are required for malignant tumors to develop (Harris, 1991). Furthermore, the specific mutant cells that are involved in tumor development are themselves subject to many secondary influences (Ashby, 1992). Consequently, the specific mechanisms responsible for the induction and/or expression of these mutant cells are not always easily or well defined. Since epidemiological data show an increase in the number of cancers in people involved in agricultural production with the use of pesticides (Bolognesi, 2003), the International Agency for Cancer Research (IARC) has reviewed the potential carcinogenicity of a wide range of insecticides, fungicides, herbicides and other similar compounds (IARC, 2002). Fifty-six pesticides have been classified as carcinogenic to animals. Moreover, the importance of cancer development after environmental contamination with chemicals has been observed (Bolognesi, 2003, Snyder and Green, 2001, Water et al., 1999). Many environmental pollutants are chemical carcinogens with the capacity of inducing DNA damage, which has therefore, been proposed as a useful parameter for assessing the genotoxic properties of environmental pollution.

The aim of the present study is to evaluate the effect of pyrethroids on rat lymphocyte DNA. The influence of low and high doses of type I (cypermethrin, CY) and type II (permethrin, PERM) pyrethroids on DNA, was assessed by comet assay. The influence of exposition to both PERM and Vitamins E and C was studied on lymphocytes and erythrocytes from rats. Data on lipid peroxidation, activity of antioxidant erythrocyte enzymes (glutathione peroxidase, catalase and superoxide dismutase) and osmotic fragility are presented.

Section snippets

Chemicals

Technical grade (62.8:37.2, trans:cis; 92.4% purity) (R,S)α-cyano-3-phenoxybenzyl(1R,S)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate, CY, (NRDC 149) and technical grade (75:25, trans:cis; 94% purity) 3-phenoxybenzyl-(1R,S)-cis,trans, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate, PERM, (NRDC 143) were generously donated by Dr. A. Stefanini of ACTIVA, Milan, Italy (Scheme 1). Corn oil, glutathione reductase, and NADPH, were obtained from Sigma St. Louis, MO,

General findings

Rats treated daily for 60 days with low and high doses of CY and PERM by intragastric tubing showed no signs of pyrethroid poisoning or gross behavioral abnormalities throughout the experimental period. Similar behaviour was observed in rats treated for 22 days with increased doses of PERM ± Vitamins E and C. Food and water consumption was not significantly affected (data not shown).

Data on body weight in rats treated with PERM and PERM + vitamins, and in untreated ones (C) are reported in Fig.

Discussion

Synthetic pyrethroids are used preferentially to organophosphates and organochlorines since they have high effectiveness for a wide range of insects, low toxicity to mammals and birds, and rapid biodegradibility (Aldridge, 1990, Vijverberg and Van Den Bercken, 1990, Ray, 1991). Nevertheless, the increased use of these pesticides increases the risk of environmental contamination and the ensuing intoxication of non-target organisms in different ecosystems (Bolognesi, 2003). Moreover, different

Acknowledgements

This work was supported by a University of Camerino fund (Progetto Strategico di Ateneo) to G.F.

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