Tomizawa M, Miyamoto T, Kato H, Otsu H
Division of Radiation Medicine, National Institute of Radiological Sciences, Chiba, Japan.
J Radiat Res. 2000 Jun;41(2):151-61. doi: 10.1269/jrr.41.151.
To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD50/60) was 42.2 +/- 0.25 Gy (standard error) for X-rays, and 22.7 +/- 0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD50/60. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure.
为评估碳离子对肝脏的急性期损伤，在三分之二部分肝切除术后，对BALB/c小鼠进行碳离子或X射线照射，并跟踪其存活情况。X射线的60天内50%致死剂量（LD50/60）为42.2±0.25 Gy（标准误差），碳离子为22.7±0.25 Gy。根据LD50/60计算，碳离子的相对生物效应（RBE）为1.86（95%置信区间：1.69 - 2.04）。接受更高剂量照射的小鼠，60 Gy的X射线或24 Gy的碳离子，其血清氨水平显著高于正常，血清白蛋白水平低于正常，提示肝衰竭是死亡原因。碳离子照射的小鼠肝细胞显示核固缩和核溶解，X射线照射的小鼠肝细胞显示点状坏死，提示核损伤。接受X射线或碳离子LD50照射的小鼠，其溴脱氧尿苷（BrdU）标记指数和有丝分裂指数显著低于对照组。BrdU和长春新碱治疗均显示，照射后合成DNA的肝细胞均未完成有丝分裂，表明细胞停滞于G2期。照射小鼠的肝脏重量随剂量显著下降。碳离子和X射线均直接损伤肝细胞并抑制肝脏再生，导致致命性肝衰竭。
