Mutagenicity and genotoxicity of isatin in mammalian cells in vivo.
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 comet assay and the micronucleus test. Three doses (50, 100, and 150mg/kgb.w.) were administered to mice via gavage. Doses were selected according to the LD(50) of isatin, estimated in a preliminary test to be 1g/kgb.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 150mg/kgb.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 (150mg/kgb.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.
Department of General Biology, Biological Sciences Center, Londrina State University, UEL, PR, Brazil.
Priscila de Matos
Pde M
Cândido-Bacani
Mariana Bisarro
MB
dos Reis
Juliana Mara
JM
Serpeloni
Tamara Regina
TR
Calvo
Wagner
W
Vilegas
Eliana Aparecida
EA
Varanda
Ilce Mara de Syllos
IM
Cólus
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D007510:Isatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D008856:Microscopy, Fluorescence; D009152:Mutagenicity Tests; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D007510:Isatin