Dewey W C, Li X L, Wong R S
Radiation Oncology Research Laboratory, University of California, San Francisco 94143-0806.
Radiat Res. 1990 Jun;122(3):268-74.
Synchronous Chinese hamster ovary cells were treated in G1 or S phase with cycloheximide or procaine hydrochloride before and during heating at 43 degrees C. Cycloheximide and procaine apparently act by different mechanisms, with cycloheximide inhibiting protein synthesis and procaine hydrochloride supposedly affecting cellular membranes. Both agents, however, modify the heat damage expressed as chromosomal aberrations, cell killing, or division delay. Furthermore, the approximately twofold protection with cycloheximide treatment or twofold sensitization with procaine treatment is the same for the three end points and for heating during either G1 or S phase. However, heat induces chromosomal aberrations observed in metaphase when cells are heated in S phase but not when they are heated in G1. Finally, for the three end points, the activation energy is about 140-152 kcal/mol. Therefore, heat may induce a common intracellular phenomenon involving protein denaturation or aggregation that is responsible for the damage observed by division delay, chromosomal aberrations, and cell-killing. There are great differences in division delay induced during the cell cycle by heat or radiation. Division delay is the same when cells are heated in the relatively heat-resistant G1 phase or the relatively heat-sensitive S phase, with about 15 min of delay for 1 min of heating at 43 degrees C. This contrasts with the increase in division delay observed when cells are irradiated in the relatively radioresistant S phase compared with the relatively radiosensitive G1 phase. Quantitatively, division delay for a treatment that reduces survival to about 0.1 is 15 or 25 h for heating in S or G1, respectively, compared with only 6 or 1.5 h for irradiation in S or G1, respectively.
将同步化的中国仓鼠卵巢细胞在G1期或S期用环己酰亚胺或盐酸普鲁卡因处理，处理时间为43℃加热之前及加热过程中。环己酰亚胺和普鲁卡因的作用机制显然不同，环己酰亚胺抑制蛋白质合成，而盐酸普鲁卡因据推测影响细胞膜。然而，这两种试剂都能改变以染色体畸变、细胞杀伤或分裂延迟表示的热损伤。此外，环己酰亚胺处理带来的约两倍的保护作用或普鲁卡因处理带来的约两倍的增敏作用，对于三个终点以及在G1期或S期加热来说都是相同的。然而，当细胞在S期加热时，热会诱导在中期观察到的染色体畸变，而在G1期加热时则不会。最后，对于三个终点来说，活化能约为140 - 152千卡/摩尔。因此，热可能诱导一种涉及蛋白质变性或聚集的常见细胞内现象，这种现象是导致通过分裂延迟、染色体畸变和细胞杀伤所观察到的损伤的原因。热或辐射在细胞周期中诱导的分裂延迟存在很大差异。当细胞在相对耐热的G1期或相对热敏的S期加热时，分裂延迟是相同的，在43℃加热1分钟会延迟约15分钟。这与在相对抗辐射的S期与相对辐射敏感的G1期照射细胞时观察到的分裂延迟增加形成对比。从数量上看，对于将存活率降低到约0.1的处理，在S期或G1期加热时的分裂延迟分别为15或25小时，而在S期或G1期照射时分别仅为6或1.5小时。
