Omar R A, Yano S, Kikkawa Y
Cancer Res. 1987 Jul 1;47(13):3473-6.
Relative cell survival and activity of the free radical scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase were measured in cloned normal (MEA) and SV40-transformed (SVMEA) mouse embryo cells exposed at 44 degrees C for 0-3 h. At 37 degrees C, all three enzymes were 2-5 times higher in MEA than in SVMEA. Hyperthermia did not significantly alter enzyme levels in either cell line but selectively reduced transformed cell survival to less than 5% while relative survival of normal cells remained above 75%. The latter, however, could be reduced to 25% when normal cells were pretreated with 3 mM diethyldithiocarbamate, an inhibitor of copper- and zinc-containing superoxide dismutase. Similar treatment rendered SVMEA extremely thermosensitive. On the other hand, sublethal heat treatment (15 min at 45 degrees C) of cultured cells resulted in a relative thermal resistance upon subsequent exposure to 45 degrees C for 1-4 h. This induced thermotolerance was associated with a rise in antioxidant enzyme levels and both became significant only 4-6 h after the initial heat treatment. Induced enzyme and thermotolerance levels in transformed cells remained, nonetheless, far below those of normal cells. The data show that inherent (in MEA) as well as induced (in SVMEA) thermotolerance is associated with high antioxidant enzyme levels while the reverse is true in the case of inherent (in SVMEA) and induced (in MEA) thermosensitivity. These findings suggest that increased production of oxygen free radicals may be involved in hyperthermic cell injury, which then becomes a function of basal or inducible levels of antioxidant enzymes. Induction of the latter by hyperthermia is apparently inefficient in transformed cells making them more vulnerable. Enzyme induction seems also to require a lag period of 4-6 h suggesting the possible involvement of an intermediate inducer(s) at molecular level. The so-called heat shock proteins may be candidates for such a role.
在44℃下暴露0 - 3小时的克隆正常（MEA）和SV40转化（SVMEA）小鼠胚胎细胞中，测定了自由基清除酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的相对细胞存活率和活性。在37℃时，MEA中这三种酶的含量比SVMEA高2 - 5倍。热疗并未显著改变两种细胞系中的酶水平，但选择性地将转化细胞的存活率降低至5%以下，而正常细胞的相对存活率仍高于75%。然而，当正常细胞用3 mM二乙基二硫代氨基甲酸盐（一种含铜和锌的超氧化物歧化酶抑制剂）预处理时，其存活率可降至25%。类似的处理使SVMEA对热极度敏感。另一方面，培养细胞的亚致死热疗（45℃下15分钟）导致随后暴露于45℃ 1 - 4小时时有相对耐热性。这种诱导的热耐受性与抗氧化酶水平的升高有关，并且两者仅在初始热疗后4 - 6小时才变得显著。然而，转化细胞中诱导的酶和热耐受性水平仍远低于正常细胞。数据表明，固有（MEA中）以及诱导（SVMEA中）的热耐受性与高抗氧化酶水平相关，而固有（SVMEA中）和诱导（MEA中）的热敏感性情况则相反。这些发现表明，氧自由基产生的增加可能参与了热诱导的细胞损伤，而这随后成为抗氧化酶基础水平或可诱导水平的一个函数。热疗对转化细胞中后者的诱导显然效率低下，使其更易受损。酶诱导似乎也需要4 - 6小时的延迟期，这表明在分子水平可能涉及一种中间诱导剂。所谓的热休克蛋白可能是这种作用的候选者。
