HEAT-INDUCED LETHALITY AND CHROMOSOMAL DAMAGE IN SYNCHRONIZED CHINESE HAMSTER CELLS TREATED WITH 5-BROMODEOXYURIDINE
HEAT-INDUCED LETHALITY AND CHROMOSOMAL DAMAGE IN SYNCHRONIZED CHINESE HAMSTER CELLS TREATED WITH 5-BROMODEOXYURIDINE
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DOI：
10.1080/09553007114551421
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发表时间：
1971-01-01
期刊：
影响因子：
--
通讯作者：
NAGASAWA, H
中科院分区：
文献类型：
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作者：
DEWEY, WC;WESTRA, A;NAGASAWA, H
中国仓鼠细胞经45·5°C热处理后，在S期细胞对染色体损伤非常敏感，即对X-射线照射的细胞，当每个细胞有一个左右的畸变率时，受热细胞的存活率为37%。然而，无论是在细胞最敏感的有丝分裂期间，还是在最具抵抗力的G1期间，当细胞被加热时，这种异常频率都很低，不能解释细胞被杀死的原因。此外，在这些细胞中，大约50%的缺失发生在有丝分裂或G染色体的次级收缩处。在细胞同步化前将BUDR掺入到DNA中，只与G1期或S期的加热有相加的相互作用。这种相互作用的特点是染色体畸变和细胞杀伤的剂量-效应曲线的肩部减小。这些发现与X射线的结果形成了巨大的反差，这是因为：(1)S期是对X射线最抵抗的时期，(2)X射线诱导的染色体畸变与整个周期的细胞杀伤呈正相关，(3)将BUDR掺入DNA中与X射线具有协同作用。其特点是将给定损伤量所需的剂量减少了两倍。从这些实验中，由于它们与文献中的发现有关，提出了一种假设，即哺乳动物细胞的热灭活是由于与DNA相关的蛋白质的变性造成的。然而，在有丝分裂细胞中，纺锤体蛋白的变性似乎是最关键的。
Synchronous Chinese hamster cells exposed to heat treatments of 45·5°cwere very sensitive during S phase when chromosomal damage could account for cell killing, i.e. as for x-irradiated cells, the 37 per cent survival value for heated cells was observed when there was about one aberration per cell. However, the aberration frequency was very low and could not account for cell killing when the cells were heated, either during mitosis when they were most sensitive in terms of lethality, or during G1when they were most resistant. Furthermore, about 50 per cent of the deletions in these cells heated in mitosis or G, occurred at the secondary constriction of the X chromosome. Incorporation of BUdR into DNA prior to synchronizing the cells had only an additive interaction with heat administered during G1or S. This interaction was characterized by a reduction in the shoulder of the dose-response curves observed for both chromosomal aberrations and cell killing.These findings contrast greatly with those for x-irradiation in that, (1) the S phase is the most resistant phase to x-irradiation, (2) there is a positive correlation between x-ray induced chromosomal aberrations and cell killing throughout the cycle, and (3) incorporation of BUdR into DNA has a synergistic interaction with x-rays, characterized by a two-fold reduction in the dose required for a given amount of damage. From these experiments, as they relate to findings in the literature, the hypothesis is presented that heat inactivation of mammalian cells results from the denaturation of proteins associated with the DNA. In mitotic cells, however, denaturation of spindle protein appears to be most critical.