Milligan A J, Metz J A, Leeper D B
Int J Radiat Oncol Biol Phys. 1984 Feb;10(2):259-63. doi: 10.1016/0360-3016(84)90012-9.
If hyperthermia is to become a useful cancer therapeutic modality, normal tissue response must be thoroughly understood. The hyperthermia response of Chinese hamster intestine was studied by immersion of the exteriorized small intestine in heated tissue culture medium. After heating, the small intestine was reinserted, the incision closed, and animals observed until death. Animals exposed to 42.5 degrees, 43.5 degrees, or 44.5 degrees C intestinal hyperthermia exhibited LD50/7 values (including 95% intervals) of 56 min (52.9-59.3), 29 min (26.4-31.8), or 14 min (13.2-14.6), respectively. An Arrhenius plot of LD50/7 vs 1/T degree K exhibited an inactivation energy of 139 kcal/mole, which corresponds well with values generally reported for cellular inactivation. Hamster intestine conditioned with a sublethal exposure of 8 min at 44.5 degrees C developed thermotolerance to subsequent 44.5 degrees C hyperthermia. Thermotolerance induction was maximal by 24 hr; the LD50/7 for the second dose of hyperthermia increased from 6 min at 44.5 degrees C at zero time to 21 min at 44.5 degrees C after a treatment interval of 24 hr (thermotolerance ratio of 3.5). The LD50/7 subsequently decreased from 21 min to 12 min at 44.5 degrees C (the control value) by 96 hr. The hyperthermia response of this tissue was predicated by previous results from the Chinese hamster ovary (CHO) fibroblast cell line in tissue culture, and is also similar to several mouse normal tissues.
如果热疗要成为一种有效的癌症治疗方式,就必须彻底了解正常组织的反应。通过将外露的小肠浸入加热的组织培养基中来研究中国仓鼠小肠的热疗反应。加热后,将小肠重新插入,缝合切口,并观察动物直至死亡。暴露于42.5摄氏度、43.5摄氏度或44.5摄氏度肠道热疗的动物,其LD50/7值(包括95%区间)分别为56分钟(52.9 - 59.3)、29分钟(26.4 - 31.8)或14分钟(13.2 - 14.6)。LD50/7与1/T(开尔文温度)的阿累尼乌斯图显示失活能为139千卡/摩尔,这与通常报道的细胞失活值非常吻合。用44.5摄氏度下8分钟的亚致死暴露预处理的仓鼠小肠对随后的44.5摄氏度热疗产生了耐热性。耐热性诱导在24小时时达到最大值;第二次热疗剂量的LD50/7从零时44.5摄氏度下的6分钟增加到24小时治疗间隔后44.5摄氏度下的21分钟(耐热比为3.5)。随后,在44.5摄氏度下,LD50/7在96小时时从21分钟降至12分钟(对照值)。该组织的热疗反应与先前在中国仓鼠卵巢(CHO)成纤维细胞系组织培养中的结果一致,并且也与几种小鼠正常组织相似。