期刊
TOXICOLOGY IN VITRO
卷 25, 期 8, 页码 2048-2053出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2011.08.007
关键词
Phenstatins; Mutagenic potential; Alkaline comet assay; Chromosome aberrations; Human lymphocytes
类别
资金
- CNPq
- CAPES
- Institut Claude Bernard
- FUNCAP
- FINEP
(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the phenstatin family. This compound has been studied due to its potent cytotoxicity and ability to inhibit tubulin assembly. The present study aimed to evaluate the mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in human lymphocytes with an IC(50) value of 5.68 mu M, and therefore, concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 mu M were used for all protocols. The alkaline comet assay and chromosome aberration (CA) analysis were performed in different phases of the cell cycle (G(1), G(1)/S, transition, and G(2)), to evaluate the DNA-damaging and clastogenic effects of PHT, respectively. CA analysis was carried out in the presence or absence of colchicine to evaluate the action of PHT in the mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with drug exposure in all phases of cell cycle. Interestingly, it induced an increase in mitotic index in experimental protocols without colchicine, corroborating its action as an antitubulin agent. It also induced DNA damage and was clastogenic with drug exposure in all phases of the cell cycle, in the presence or absence of colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects in human lymphocytes. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.
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