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抗肿瘤药物硫酸长春新碱对人外周血淋巴细胞的体外遗传毒性作用

[Genotoxic effect of the antitumor agent vincristine sulfate on human peripheral blood lymphocytes in vitro].

作者信息

Nefić H, Ibrulj S

机构信息

Centar za humanu genetiku Medicinskog fakulteta, Univerziteta u Sarajevu.

出版信息

Med Arh. 1999;53(4):185-8.

Abstract

In consideration of high toxicity of cytostatic drugs and their potential mutagenic activity, this work studies the genotoxic effects of the antitumour drug Vincristine Sulfate. We analyzed preparations of human peripheral blood lymphocytes that have been exposed to different concentrations of Vincristine Sulfate in vitro. We have established that this cytostatic stimulates mitotic activity of lymphocytes at smaller concentrations (0.05 and 0.1 microgram/ml), but at higher concentration (0.5, 1.0 and 20.0 micrograms/ml) decreases proliferation of lymphocytes at significant level. It causes the appearance of irregular anaphase statuses in form of irregular distribution of chromosomes. Vincristine induces of appearance of C-mitosis that are a result of cytostatic activity of Vincristine Sulfate that blocks mitosis with prometaphase arrest. Cytostatic activity of Vincristine manifests itself as the destruction of interphase nuclei, the destruction of prophase nuclei with the destruction of chromosome mass and as the presence of chromosome material that is cut up in small pieces (chromosome pulverization). Vincristine interferes with the function of microtubules that are responsible for this mitosis and cytokinesis, and therefore influences itself on the formation of binucleated and multinucleated cells. Cytogenetic studies indicate that Vincristine induces the presence of micronuclei in lymphocyte's cells, while a higher concentration of Vincristine induces the presence of a large number of micronuclei at lymphocyte called multimicronuclei. Numerical chromosome aberrations are aneuploidy and poluploidy.

摘要

鉴于细胞毒性药物的高毒性及其潜在的诱变活性,本研究探讨抗肿瘤药物硫酸长春新碱的遗传毒性作用。我们分析了体外暴露于不同浓度硫酸长春新碱的人外周血淋巴细胞制剂。我们发现,这种细胞抑制剂在较低浓度(0.05和0.1微克/毫升)时刺激淋巴细胞的有丝分裂活性,但在较高浓度(0.5、1.0和20.0微克/毫升)时显著降低淋巴细胞的增殖。它导致染色体不规则分布形式的不规则后期状态的出现。长春新碱诱导C-有丝分裂的出现,这是硫酸长春新碱细胞抑制活性的结果,其通过前中期停滞阻断有丝分裂。长春新碱的细胞抑制活性表现为间期核的破坏、前期核的破坏以及染色体物质被切割成小碎片(染色体粉碎)。长春新碱干扰负责这种有丝分裂和胞质分裂的微管功能,因此影响双核和多核细胞的形成。细胞遗传学研究表明,长春新碱诱导淋巴细胞细胞中出现微核,而较高浓度的长春新碱在淋巴细胞中诱导大量微核的出现,称为多微核。染色体数目畸变包括非整倍体和多倍体。

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