Programa de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, Canoas, RS, Brazil.
Mutat Res. 2010 Feb;696(2):139-43. doi: 10.1016/j.mrgentox.2010.01.002. Epub 2010 Jan 18.
Recent studies have added paclitaxel (PAC) to traditional cisplatin (CIS) regimen to treat squamous cell carcinoma of the head and neck. The target of these antineoplastic agents is nuclear DNA for CIS and microtubules for PAC, although it is not restricted to malignant cells. In this study, the genotoxicity of the combined treatment of PAC and CIS was investigated using the standard version of the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Quantitative and qualitative genotoxic effects of these compounds were estimated by comparing wing spot frequencies in marker-heterozygous to balancer-heterozygous flies. Two different concentrations of PAC (0.0025 and 0.005mM) and CIS (0.025 and 0.05mM) as well as combinations of them were employed. The results demonstrated that the spindle poison PAC alone was not genotoxic in this test system, while CIS was able to induce a high incidence of DNA damage in both genotypes, mainly related to somatic recombination. The data obtained for the combined treatments showed that its genotoxicity varied with the concentrations used. In small concentrations the number of total spots induced by combination was reduced in relation to CIS 0.025mM just for marker-heterozygous flies, showing that somatic recombination was the prevalent event involved. At higher concentrations the combined treatment showed significant reductions in the frequencies of large single spots, for both genotypes, and twin spots for marker-heterozygous flies, but did not significantly reduce the total spots frequency in either genotype. The data suggest that aneugenic activity of PAC could be responsible for the reduction in the genotoxicity of CIS.
最近的研究已经将紫杉醇（PAC）添加到传统的顺铂（CIS）方案中，用于治疗头颈部鳞状细胞癌。这些抗肿瘤药物的靶点是 CIS 的核 DNA 和 PAC 的微管，但不限于恶性细胞。在这项研究中，使用黑腹果蝇的标准翼体突变和重组测试（SMART）版本研究了 PAC 和 CIS 联合治疗的遗传毒性。通过比较标记杂合子与平衡杂合子果蝇的翅膀斑点频率来估计这些化合物的定量和定性遗传毒性作用。使用了两种不同浓度的 PAC（0.0025 和 0.005mM）和 CIS（0.025 和 0.05mM）以及它们的组合。结果表明，单独的纺锤体毒物 PAC 在该测试系统中没有遗传毒性，而 CIS 能够在两种基因型中诱导高发生率的 DNA 损伤，主要与体细胞重组有关。对于联合处理获得的数据表明，其遗传毒性随所用浓度而变化。在小浓度下，与 CIS 0.025mM 相比，组合诱导的总斑点数量减少，仅对于标记杂合子果蝇，表明体细胞重组是涉及的主要事件。在较高浓度下，联合处理显示出两种基因型中大单个斑点和标记杂合子果蝇的双斑点频率显著降低，但在任何一种基因型中均未显著降低总斑点频率。数据表明，PAC 的着丝粒毒物活性可能导致 CIS 的遗传毒性降低。
