Millar J L, Blackett N M, Hudspith B N
Cell Tissue Kinet. 1978 Sep;11(5):543-53. doi: 10.1111/j.1365-2184.1978.tb00826.x.
It is known that pretreatment of mice with bacterial endotoxin and certain stathmokinetic agents between 1 and 3 days prior to exposure to ioninzing radiation reduce radiation lethality. In this communication it is shown that pretreatment with cytosine arabinoside, methotrexate, nortestosterone and chlorambucil reduces radiation (1000 rad) induced lethality. This reduction can be ascribed to enhanced regeneration of the haemopoietic system in pretreated animals and not to increased survival of colony-forming cells (CFU) in these animals. Regeneration of CFUs was underway within 24 hr after 900 rad in the pretreated mice but did not start until day 3 in mice treated with gamma radiation only. Two agents, namely radiation itself (either 75 or 150 rad) and busulphan (10 mg/kg) did not reduce the lethal effects of subsequent gamma irradiation nor enhance the regeneration of CFUs, even though radiation, like the protective cytosine arabinoside, induces early CFUs proliferation. The administration of nucleoside precursors of DNA enhanced regrowth of haemopoietic stem cells to an extent comparable with that of the most effective pretreatment, cytosine arabinoside. It is postulated that drugs like cytosine arabinoside operate by causing cell death, providing a source of DNA that con enhance the regrowth of surviving stem cells in the bone marrow.
已知在暴露于电离辐射前1至3天，用细菌内毒素和某些细胞分裂抑制剂对小鼠进行预处理可降低辐射致死率。在本报告中表明，用阿糖胞苷、甲氨蝶呤、诺睾酮和苯丁酸氮芥进行预处理可降低辐射（1000拉德）诱导的致死率。这种降低可归因于预处理动物造血系统再生增强，而不是这些动物中集落形成细胞（CFU）存活率的增加。预处理小鼠在900拉德照射后24小时内CFU开始再生，但仅接受γ射线照射的小鼠直到第3天才开始。两种药剂，即辐射本身（75或150拉德）和白消安（10毫克/千克），既没有降低随后γ射线照射的致死效应，也没有增强CFU的再生，尽管辐射与具有保护作用的阿糖胞苷一样，可诱导早期CFU增殖。给予DNA的核苷前体可使造血干细胞的再生长增强到与最有效的预处理药物阿糖胞苷相当的程度。据推测，像阿糖胞苷这样的药物通过导致细胞死亡起作用，提供一种DNA来源，可增强骨髓中存活干细胞的再生长。
