Jirtle R L, Michalopoulos G, Strom S C, DeLuca P M, Gould M N
Br J Cancer Suppl. 1984;6:197-201.
We have developed an in vivo clonogenic assay system for parenchymal hepatocytes which has enabled us to investigate the reproductive survival and repair capacity of liver cells exposed to genotoxic agents. In this report we present our results with hepatocytes irradiated 60Co and neutrons. The survival curve for parenchymal hepatocytes enzymatically dispersed 30 min after exposure to 60Co has a D0 value of 2.7 Gy and an extrapolation number insignificantly different from unity. However, when the hepatocytes were allowed to remain in situ for 24 h before being assayed for survival, the extrapolation number significantly increased to 2.3, whereas the D0 value remained unchanged. Therefore, normal parenchymal hepatocytes in G0 are able to repair potentially lethal damage (PLD) after exposure to 60Co and this repair phenomenon is expressed solely as an increase in the n value. In contrast, with hepatocytes exposed to 14.3 MeV neutrons, the survival curve is exponential with a D0 value of 1.7 Gy regardless of whether the cells remained in situ for 30 min or 24 h before the assessment of their reproductive survival. A comparison of the 60Co and neutron survival curves, where 24 h is allowed for PLD repair to occur, demonstrates that the RBE of neutrons for hepatocytes increases with decreasing dose and equals 4.2 at 50 cGy. The radioprotective agent WR-2721 was shown to act as a dose modifying agent with a DMF of 2.1, implying that it may be of potential clinical value as a radiation hepato-protective drug.
我们已经开发出一种用于实质肝细胞的体内克隆形成测定系统，该系统使我们能够研究暴露于基因毒性剂的肝细胞的生殖存活和修复能力。在本报告中，我们展示了用60Co和中子照射肝细胞的结果。暴露于60Co 30分钟后酶解分散的实质肝细胞的存活曲线，其D0值为2.7 Gy，外推数与1无显著差异。然而，当肝细胞在测定存活前原位保留24小时时，外推数显著增加至2.3，而D0值保持不变。因此，处于G0期的正常实质肝细胞在暴露于60Co后能够修复潜在致死性损伤（PLD），并且这种修复现象仅表现为n值的增加。相比之下，对于暴露于14.3 MeV中子的肝细胞，无论细胞在评估其生殖存活前原位保留30分钟还是24小时，存活曲线均为指数型，D0值为1.7 Gy。对允许进行PLD修复24小时的60Co和中子存活曲线的比较表明，中子对肝细胞的相对生物效应（RBE）随剂量降低而增加，在50 cGy时等于4.2。放射防护剂WR-2721被证明是一种剂量修饰剂，剂量修饰因子（DMF）为2.1，这意味着它作为一种辐射肝保护药物可能具有潜在的临床价值。
