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首页> 外文期刊>Journal of applied toxicology >Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells
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Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells

机译:氨茶碱和诺考达唑对小鼠骨髓细胞遗传毒性作用机理的分子细胞遗传学评估

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摘要

The mechanism of genotoxic potential of the cancer chemotherapeutic drugs amsacrine and nocodazole in mouse bone marrow was investigated using a micronucleus test complemented by fluorescence in situ hybridization assay with mouse centromeric and telomeric DNA probes. In animals treated with different doses of amsacrine (0.5-12 mg kg-1), the frequencies of micronucleated polychromatic erythrocytes increased significantly after treatment with 9 and 12 mg kg-1. A statistically significant increase in micronuclei frequency was also detected for 75 mg kg-1 nocodazole (two exposures, spaced 24 h apart). Both compounds caused significant suppressions of erythroblast proliferation at higher doses. Furthermore, the present study demonstrated for the first time that amsacrine has high incidences of clastogenicity and low incidences of aneugenicity whereas nocodazole has high incidences of aneugenicity and low incidences of clastogenicity during mitotic phases in vivo. The assay also showed that chromosomes can be enclosed in the micronuclei before and after centromere separation. Therefore, the clinical use of these genotoxic drugs must be weighed against the risks of the development of chromosomal aberrations in cancer patients and medical personnel exposed to drug regimens that include these chemicals.
机译:使用微核试验,并用小鼠着丝粒和端粒DNA探针进行荧光原位杂交分析,研究了癌症化学治疗药物氨色林和诺考达唑在小鼠骨髓中的潜在遗传毒性。在用不同剂量的氨茶碱(0.5-12 mg kg-1)治疗的动物中,用9和12 mg kg-1治疗后,微核多色红细胞的频率显着增加。对于75 mg kg-1的Nocodazole(两次暴露,间隔24小时),也检测到微核频率的统计学显着增加。两种化合物在高剂量时均能显着抑制成红细胞的增殖。此外,本研究首次证明氨色林在体内有丝分裂期具有高的致胶凝性和低的无气质性,而诺考达唑具有高的致胶质性和低致胶质性。该测定还表明,在着丝粒分离之前和之后,染色体可以被封闭在微核中。因此,必须权衡这些遗传毒性药物的临床使用与癌症患者和接触包括这些化学药品的药物治疗方案的医务人员发生染色体畸变的风险之间的关系。

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