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化学物质诱导的染色体损伤的后期-末期分析

Anaphase-telophase analysis of chromosomal damage induced by chemicals.

作者信息

Dulout F N, Olivero O A

出版信息

Environ Mutagen. 1984;6(3):299-310. doi: 10.1002/em.2860060306.

DOI:10.1002/em.2860060306
PMID:6428871
Abstract

Three main aspects involved in the chemical induction of anaphase-telophase aberrations in the first mitosis after treatment were analyzed: 1) the relationship between the frequency of anaphase-telophase aberrations and the time of fixation after treatment; 2) the dose-response relationships; and 3) the proliferative rate of cells exposed to chemicals which interact with DNA by different mechanisms. Experiments were carried out using Chinese hamster ovary (CHO) cells. The compounds examined were adriamycin (ADR) and mitomycin C (MMC). The frequency of cells with chromatin bridges or with lagging chromosomes as well as the mitotic index was determined in each experiment. The results obtained showed that 1) chromatin bridges and lagging chromosomes are apparently induced during the S period of the previous interphase; 2) the increase in the cytotoxicity index (inferred from the mitotic index) and the frequency of cells with chromatin bridges and lagging chromosomes were proportional to the treatment lapse and to the dose employed; and 3) the effect of ADR on cell growth differs from the effect of MMC. While ADR decreased the mitotic activity of cells in logarithmic growth phase, MMC induced mitotic delay. In accordance with these results, the occurrence of chromatin bridges in anaphase-telophase could be explained by the induction of chromosome stickiness and, to a lesser extent, by the induction of exchange-type aberrations. On the other hand, lagging chromosomes seem to be the result of chromatid or chromosome breaks because the lagging chromosomes observed were primarily, if not all, fragments and not whole chromosomes. Our evaluation of the anaphase-telophase test indicates that it is very sensitive method for the detection of chemical clastogens, but other factors, such as mitotic depression, must be taken into account to avoid false-negative results.

摘要

分析了处理后第一次有丝分裂中化学诱导后期 - 末期畸变所涉及的三个主要方面:1)后期 - 末期畸变频率与处理后固定时间的关系;2)剂量 - 反应关系;3)通过不同机制与DNA相互作用的化学物质处理的细胞的增殖率。使用中国仓鼠卵巢(CHO)细胞进行实验。所检测的化合物为阿霉素(ADR)和丝裂霉素C(MMC)。在每个实验中测定具有染色质桥或落后染色体的细胞频率以及有丝分裂指数。获得的结果表明:1)染色质桥和落后染色体显然是在前一个间期的S期诱导产生的;2)细胞毒性指数(由有丝分裂指数推断)以及具有染色质桥和落后染色体的细胞频率的增加与处理时间和所用剂量成正比;3)ADR对细胞生长的影响不同于MMC的影响。ADR降低对数生长期细胞的有丝分裂活性,而MMC诱导有丝分裂延迟。根据这些结果,后期 - 末期染色质桥的出现可以通过染色体粘性的诱导来解释,在较小程度上也可以通过交换型畸变的诱导来解释。另一方面,落后染色体似乎是染色单体或染色体断裂的结果,因为观察到的落后染色体主要(如果不是全部)是片段而不是整条染色体。我们对后期 - 末期试验的评估表明,它是检测化学断裂剂的非常敏感的方法,但必须考虑其他因素,如有丝分裂抑制,以避免假阴性结果。

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