Travis E L, Meistrich M L, Finch-Neimeyer M V, Watkins T L, Kiss I
Radiat Res. 1985 Aug;103(2):219-31.
The radioprotective effect of WR-2721 on late damage after whole thorax irradiation has been studied after split doses of radiation using the standard death and breathing rate assays at monthly intervals between 3 and 15 months after irradiation, as well as two biochemical measurements of injury at 15 months, hydroxyproline (HP), an indicator of tissue fibrosis, and DNA content, an indicator of tissue cellularity. A comparison of HP/lung and breaths per minute (BPM) in each dose group in the WR-2721 and non-WR-2721-treated mice 15 months after irradiation showed that the relationship between these two assays of late lung injury was not the same. There were large dose-related increases in breathing rate corresponding to relatively small changes in HP in the lungs of mice given radiation alone. In contrast, the mice given WR-2721 before irradiation showed large dose-related increases in HP/lung, but BPM remained relatively constant independent of dose. These data suggest then that changes in breathing rate and deaths later than 9 months after whole lung irradiation may not be due to collagen accumulation in the lung. WR-2721 did protect better against late lung functional changes (protection factors (PF) = 1.6) and late deaths (PF = 1.51) than against earlier changes in these same assays (PF = 1.4 and 1.28, respectively). Although the earlier-appearing injury after whole thoracic irradiation is most likely related to lung damage with deaths and increases in breathing rate resulting from pneumonitis, the cause of the late-appearing functional injury in the lung after radiation is not clear. Thus protection of late lung damage measured from either lethality or breathing rate is not related to the prevention of lung fibrosis.
使用标准的死亡和呼吸频率测定法，在照射后3至15个月期间每月进行一次间隔，研究了WR-2721对全胸照射后晚期损伤的辐射防护作用，以及在15个月时进行的两项损伤生化测量，即羟脯氨酸（HP）（组织纤维化指标）和DNA含量（组织细胞性指标）。对WR-2721处理组和未处理组小鼠在照射后15个月时各剂量组的HP/肺与每分钟呼吸次数（BPM）进行比较，结果显示这两种晚期肺损伤检测方法之间的关系并不相同。单独接受辐射的小鼠肺部，呼吸频率有与剂量相关的大幅增加，而HP变化相对较小。相比之下，照射前给予WR-2721的小鼠，HP/肺有与剂量相关的大幅增加，但BPM相对保持恒定，与剂量无关。这些数据表明，全肺照射后9个月以后的呼吸频率变化和死亡可能并非由于肺中胶原蛋白积累所致。与这些相同检测方法中早期变化（保护因子（PF）分别为1.4和1.28）相比，WR-2721对晚期肺功能变化（保护因子（PF）=1.6）和晚期死亡（保护因子（PF）=1.51）的防护效果更好。虽然全胸照射后较早出现的损伤很可能与肺损伤有关，死亡和呼吸频率增加是由肺炎引起的，但辐射后肺中晚期出现的功能损伤原因尚不清楚。因此，从致死率或呼吸频率测量的晚期肺损伤防护与预防肺纤维化无关。
