Rofstad E K, Brustad T
Int J Hyperthermia. 1985 Jan-Mar;1(1):85-96. doi: 10.3109/02656738509029276.
One uncloned and five cloned cell lines were isolated from a single human melanoma xenograft in passage 39 in athymic mice. Cells from passages 7-12 in vitro were heated at 42.5, 43.5 or 44.5 degrees C and the colony forming ability of the cells was assayed in soft agar. The six cell lines showed individual and characteristic responses to heat treatment. The D0 values of the survival curves were in the ranges 76 +/- 5 to 131 +/- 13 min (42.5 degrees C), 12.5 +/- 1.1 to 22.2 +/- 1.9 min (43.5 degrees C) and 9.4 +/- 1.0 to 15.6 +/- 1.5 min (44.5 degrees C). Cells from all lines developed thermotolerance during protracted treatments at 42.5 degrees C. Thermotolerance was also studied by giving the cells a priming treatment of 43.5 degrees C for 90 min and then, after different fractionation intervals at 37 degrees C, second graded treatments at 43.5 degrees C. Thermotolerance ratio (TTR), i.e. the ratio of the slopes of the survival curves for preheated and single-heated cells, was used as a quantitative measure of the thermotolerance. Thermotolerance developed rapidly for all lines, reached a maximum at 12 or 16 h, and then decayed slowly. Maximum TTR varied among the lines from 4.2 +/- 0.5 to 6.0 +/- 0.9, i.e. within a factor of about 1.4. The survival curves and the TTR-curve for the uncloned line were positioned in the midst of those of the cloned lines. A linear correlation between maximum TTR and heat sensitivity was found for the six lines; maximum TTR decreased with increasing D0 value at 43.5 degrees C. Nevertheless, the lines which were most resistant before thermotolerance developed were also most resistant at maximum thermotolerance.
从无胸腺小鼠传代39次的单一人类黑色素瘤异种移植瘤中分离出1个未克隆的细胞系和5个克隆的细胞系。将体外培养第7 - 12代的细胞在42.5、43.5或44.5摄氏度下加热，然后在软琼脂中检测细胞的集落形成能力。这6个细胞系对热处理表现出各自独特的反应。存活曲线的D0值范围为76±5至131±13分钟（42.5摄氏度）、12.5±1.1至22.2±1.9分钟（43.5摄氏度）和9.4±1.0至15.6±1.5分钟（44.5摄氏度）。所有细胞系的细胞在42.5摄氏度的长时间处理过程中都产生了热耐受性。还通过对细胞进行43.5摄氏度90分钟的预适应处理，然后在37摄氏度下经过不同的分级间隔后，再进行43.5摄氏度的第二次分级处理来研究热耐受性。热耐受比（TTR），即预热细胞和单次加热细胞存活曲线斜率的比值，被用作热耐受性的定量指标。所有细胞系的热耐受性发展迅速，在12或16小时达到最大值，然后缓慢衰减。最大TTR在各细胞系之间从4.2±0.5到6.0±0.9不等，即相差约1.4倍。未克隆细胞系的存活曲线和TTR曲线位于克隆细胞系的曲线中间。发现这6个细胞系的最大TTR与热敏感性之间存在线性相关性；在43.5摄氏度时，最大TTR随着D0值的增加而降低。然而，在热耐受性产生之前最耐药的细胞系在最大热耐受性时也是最耐药的。
