Genética toxicológica da chalcona sulfonamida (CPN): evidências de genoto-xicidade e antimutagenicidade em diferentes sistemas-teste in vivo e in vitro
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2015-03-20
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Universidade Federal de Goiás
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Sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In the present study, we investigated the biological effects of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) through bioindicators of genetic damage in bacteria, animal and human. In the Ames Mutagenicity Test, CPN did not significantly increase the number of His+ revertants in Salmonella typhimurium tester strains TA98 and TA100 at all doses tested (p > 0.05). However, CPN presented a moderate mutagenic and toxic profile, due to dose-response relationship observed at all doses tested for TA98 and TA100 strains. In the antimutagenic evaluation of Ames Test, CPN presented antimutagenic activity at all doses tested in TA98 strain (p < 0.05). In the TA100 strain, CPN showed antimutagenic activity in doses over 50 μg/plate. In the Micronucleus Test, the results demonstrated that CPN increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, at all doses tested, demonstrating mutagenic effect of this compound. A decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at 24 h and 48 h, indicating the cytotoxic action of CPN. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at all doses tested in 24 h, demonstrating antimutagenic action (p < 0.05). Also, there was a decrease in the frequency of MNPCE at all tested doses in 48 h, but this decrease was not significant (p > 0.05). Additionally, CPN co-administered with MMC increased PCE/NCE ratio at all doses tested, in both times, demonstrating its anticytotoxic effect. In the Comet Assay, CPN significantly increased the percentage of DNA damages at all doses tested (p < 0.05), demonstrating genotoxic activity. In the analysis of cell cycle kinetics, CPN did not induce significant changes in the cell cycle phases G0/G1, S and G2/M of peripheral blood mononuclear cells (PBMC) (p > 0.05). However, doses of 256 and 512 μmol/L of the CPN presented a significant increase in the percentage of cells in sub-G1 (p < 0.05), which is indicative of apoptosis, indicating cytotoxic action. For apoptosis and necrosis detection using Annexin V/Propidium Iodide stain, CPN showed a cytotoxic effect by inducing late apoptosis and necrosis. Thus, according to tests performed CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities.
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SILVA, C. R. Genética toxicológica da chalcona sulfonamida (CPN): evidências de genoto-xicidade e antimutagenicidade em diferentes sistemas-teste in vivo e in vitro. 2015. 88 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2015.