Sorokina N I, Pushkareva N B, Nikolsky A V, Denisenko M F, Filippovich I V
Institute of Biophysics, Department of Health, Moscow, Russia.
Int J Radiat Biol. 1992 Nov;62(5):603-12. doi: 10.1080/09553009214552521.
Ionizing radiation, glucocorticosteroids and chemical inducers of differentiation (CID) are cytotoxic to thymocytes, and induce internucleosomal DNA fragmentation. Tissue cAMP levels in thymi of irradiated mice were significantly elevated as early as 30 min post-irradiation. In contrast, cAMP content in the liver was not changed significantly up to 1 h post-irradiation, and then some decrease occurred. Irradiation of isolated thymocytes gave essentially the same results as after irradiation of animals, and the elevation in cAMP 30 min after the irradiation, DNA fragmentation and cell death were linearly related to the dose up to 2.5 Gy. The maximal induction of cAMP level occurs in the fractions of radiosensitive cortical thymocytes. In thymocytes all CID tested also induced the increase in cAMP level with concomitant DNA fragmentation. Unlike ionizing radiation, UVC light did not induce cAMP accumulation and DNA fragmentation in thymocytes. Treatment of UV-irradiated cells with But2 cAMP did not result in an increase in DNA fragmentation. Ionizing radiation induced DNA fragmentation and cell death can be prevented by adding the protein kinases inhibitor H-7. Theophylline was shown to reduce the cAMP response, DNA fragmentation and cell death in gamma-irradiated thymocytes, suggesting that the accumulation of cAMP may be partly related to adenosine receptor sites.
电离辐射、糖皮质激素和分化化学诱导剂（CID）对胸腺细胞具有细胞毒性，并诱导核小体间DNA片段化。受辐照小鼠胸腺中的组织cAMP水平早在辐照后30分钟就显著升高。相比之下，肝脏中的cAMP含量在辐照后1小时内没有显著变化，随后出现了一些下降。对分离的胸腺细胞进行辐照得到的结果与对动物辐照后的结果基本相同，辐照后30分钟cAMP的升高、DNA片段化和细胞死亡与高达2.5 Gy的剂量呈线性相关。cAMP水平的最大诱导发生在放射敏感的皮质胸腺细胞部分。在胸腺细胞中，所有测试的CID也诱导cAMP水平升高并伴随DNA片段化。与电离辐射不同，紫外线C（UVC）光不会诱导胸腺细胞中cAMP积累和DNA片段化。用丁酰环磷腺苷（But2 cAMP）处理紫外线照射的细胞不会导致DNA片段化增加。添加蛋白激酶抑制剂H-7可以预防电离辐射诱导的DNA片段化和细胞死亡。已证明氨茶碱可降低γ射线辐照的胸腺细胞中的cAMP反应、DNA片段化和细胞死亡，这表明cAMP的积累可能部分与腺苷受体位点有关。
