Pessoa C, Vieira F M A C, Lemos T G, Moraes M O, Lima P D L, Rabenhorst S H B, Leyva A, Burbano R R
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
Teratog Carcinog Mutagen. 2003;Suppl 1:215-20. doi: 10.1002/tcm.10075.
Inadequate doses or prolonged chemotherapy can be cytotoxic or genotoxic to cancer patients, increasing the risk for the development of a second cancer, particularly acute leukemia. The association between therapeutic and genotoxic properties of oncocalyxone A (Onco A), make cytotoxic tests (mitotic index and chromosomal aberrations) fundamental in the accompaniment of the effects of this active compound. Therefore, the aim of the present study was to determine the genotoxic action of Onco A in vitro, during different phases of the cell cycle, utilizing primary cultures of lymphocytes of healthy individuals. The results showed that Onco A is cytotoxic during the cell cycle phases G1, G1/S, and S, however, not in G2. Onco A did not demonstrate a genotoxic effect in any of the cell cycle phases at the concentration studied. It is concluded that during the period of exposure, this active substance inhibits DNA synthesis and consequently cell division. Therefore, the absence of such genotoxicity for Onco A in the tests performed in this study provides important information in regard to the therapeutic use of this agent. Further studies are necessary to better understand the molecular mechanism of action of Onco A.
剂量不足或化疗时间延长可能对癌症患者具有细胞毒性或基因毒性,增加患第二种癌症尤其是急性白血病的风险。癌萼酮A(Onco A)的治疗特性与基因毒性之间的关联,使得细胞毒性试验(有丝分裂指数和染色体畸变)对于监测这种活性化合物的作用至关重要。因此,本研究的目的是利用健康个体淋巴细胞的原代培养物,在细胞周期的不同阶段体外确定Onco A的基因毒性作用。结果表明,Onco A在细胞周期的G1期、G1/S期和S期具有细胞毒性,但在G2期没有。在所研究的浓度下,Onco A在任何细胞周期阶段均未表现出基因毒性作用。得出的结论是,在暴露期间,这种活性物质抑制DNA合成并因此抑制细胞分裂。因此,本研究中进行的试验中Onco A不存在这种基因毒性,为该药物的治疗用途提供了重要信息。需要进一步研究以更好地理解Onco A的分子作用机制。