Jeong Won-Il, DO Sun-Hee, Kim Tae-Hwan, Jeong Da-Hee, Hong Il-Hwa, Ki Mi-Ran, Kwak Dong-Mi, Lee Seung-Sook, Jee Young-Heun, Kim Soon-Bok, Jeong Kyu-Shik
Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea.
J Radiat Res. 2007 May;48(3):233-40. doi: 10.1269/jrr.0629.
Until now, the multiple biological effects of ionizing radiation on liver have been reported. However, there has not been any reports of fast neutron-mediated liver injuries including liver regeneration or fibrosis. Here, we described the biological effects of acute fast neutron irradiation on the liver. After the fast neutron irradiation of 0, 0.25, 1, 2, 4 and 8 Gy on mice, hepatocyte necrosis and a decrease in the total number of hepatocytes were induced dose-dependently. Binucleated hepatocytes and PCNA positive hepatocytes increased significantly at 0.25 and 1 Gy, but decreased markedly at 2, 4 and 8 Gy. The expression of cytochrome P450 2E1 (CYP2E1) showed a dose-dependent increase after fast neutron irradiation. The activation of p-Smad2/3, signaling intermediates of transforming growth factor-beta (TGF-beta), increased in hepatocytes after exposure of 0.25, 1, and 2 Gy of fast neutrons, but it was not detected in hepatic stellate cells (HSCs). In conclusion, fast neutron-induced liver damages, likely loss of hepatocytes, necrotic foci and vacuolar changes, were note on the dose dependent manner and hepatocellular regeneration were significantly diminished at doses of 2, 4 and 8Gy in a dose-dependent manner. These alterations may at least in part be associated with dose-dependent increase in CYP2E1 and p-Smad2/3. These results show promise as an approach for the treatment of fast neutrons on liver tumors and in the study of pathogenesis regarding the fast neutron-irradiated damages of the liver.
到目前为止，已经报道了电离辐射对肝脏的多种生物学效应。然而，尚未有关于快中子介导的肝脏损伤（包括肝再生或纤维化）的报道。在此，我们描述了急性快中子照射对肝脏的生物学效应。对小鼠进行0、0.25、1、2、4和8 Gy的快中子照射后，肝细胞坏死和肝细胞总数减少呈剂量依赖性。双核肝细胞和PCNA阳性肝细胞在0.25和1 Gy时显著增加，但在2、4和8 Gy时明显减少。快中子照射后，细胞色素P450 2E1（CYP2E1）的表达呈剂量依赖性增加。转化生长因子-β（TGF-β）的信号中间体p-Smad2/3在接受0.25、1和2 Gy快中子照射后的肝细胞中激活增加，但在肝星状细胞（HSC）中未检测到。总之，快中子诱导的肝脏损伤，可能表现为肝细胞丢失、坏死灶和空泡样改变，呈剂量依赖性，并且在2、4和8 Gy剂量时肝细胞再生以剂量依赖性方式显著减少。这些改变可能至少部分与CYP2E1和p-Smad2/3的剂量依赖性增加有关。这些结果有望成为治疗肝脏肿瘤的快中子方法以及研究快中子照射肝脏损伤发病机制的途径。
