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Genotoxicity of zearalenone, an estrogenic mycotoxin: DNA adduct formation in female mouse tissues
Ecole Nationale Supérieure Agrononuquc, Laboratoire de Toxicologie et Sécurité Alimenture 145 avenue de Muret, 31076 Toulouse, France
1Faculté Médecine et Dentaire, rue Avicenne, Monastir Tunisie
2To whom correspondence should be addressed
Zearalenone is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium which colonize maize, barley, oats, wheat and sorghum and have been implicated in numerous mycotoxicoses in farm animals, especially pigs. In a NTP mouse study a dose-related incidence of hepatocellular adenomas was seen in female mice. A limited number of genotoxicity assays have been conducted with zearalenone. Zearalenone was found to be negative in the Salmonella typhimurium assay. It was also negative in a eukaryotic cell mutation assay with Saccharomyces cerevisae. However, zearalenone and its estrogenic metabolites showed a positive DNA damaging effect in recombination tests with Bacillus subtilis. In this study DNA adducts in female mice and rat treated i.p or orally with zearalenone were determined using a 32p-postlabeling method. Several DNA adducts (12–15) were found in the kidney and liver of female mice treated with a single dose of zearalenone (2 mg/kg i.p. or orally). The total DNA adduct levels reached 114±37 and 1393±324 adducts/109 nucleotides respectively in kidney and liver after i.p. treatment and 548±50 adducts/109 nucleotides in liver after oral treatment. In mice ovary DNA adducts appeared only after repeated doses (1 mg/kg body wt on days 1, 5, 7, 9 and 10). The total DNA adducts after 10 days in this organ were 17±5 adducts/109 nucleotides. Some adducts were common to all organs. Others were specific to an organ. In contrast, no DNA adducts could be detected in rat organs after i.p. treatment. These results confirm the genotoxiclty of zearalenone and its ability to induce hepatocellular adenomas, rather than tumours of genital organs, in mice.
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