Mutagenicity and genotoxicity of isatin in mammalian cells in vivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Isatin (1H-indole-2,3-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Isatin and its derivatives demonstrate anticonvulsant, antibacterial, antifungal, antiviral, and anticancer properties. We evaluated the genotoxic and mutagenic effects of acute (24h) and repeated (14d) exposure to isatin in vivo. using the cornet assay and the micronucleus test. Three doses (50, 100, and 150 mg/kg b.w.) were administered to mice via gayage. Doses were selected according to the LD(50) of isatin, estimated in a preliminary test to be 1 g/kg b.w. To evaluate the results, parametric (ANOVA/Tukey) and non-parametric (Kruskal-Wallis/Dunn's post hoc test) tests were used, according to the nature of the data distribution. At all doses (50, 100 and 150 mg/kg b.w.), after acute treatment with isatin, alterations in DNA migration (comet assay) were not observed and mutagenic effects were not seen (micronucleus test on peripheral blood cells). After repeated doses, only the highest dose of isatin (150 mg/kg b.w.) induced alterations in the DNA that gave rise to micronuclei in the bone marrow and peripheral blood cells of the mice. Our results show that the mutagenic and genotoxic effects of isatin depend on dose and on period of exposure. (C) 2010 Elsevier B.V. All rights reserved.