Down J D, Laurent G J, McAnulty R J, Steel G G
Int J Radiat Biol Relat Stud Phys Chem Med. 1984 Nov;46(5):597-607. doi: 10.1080/09553008414551791.
The modification of early and late radiation damage to the mouse lung by oxygen and WR 2721 has been studied by measurement of breathing rate, lethality, pleural fluid and hydroxyproline content. Protection by hypoxia and sensitization by hyperoxia of early radiation pneumonitis were demonstrated. There was a tendency for the protective effect of WR 2721 to decrease as the breathed oxygen concentration was raised above normal levels. WR 2721 protection of the late damage was higher (PF = 1.6-1.65) than was seen for early pneumonitis (PF = 1.3-1.35) when either breathing rate or lethality were used. Protection factors (PF) gained from measurements of pleural fluid at a year after treatment were similar to those for other endpoints of late damage (PF = 1.7). In contrast, the measurement of fibrosis through determination of lung hydroxyproline at 1 year gave a somewhat lower protection factor for WR 2721. In the same experiments the degree of epilation on the dorsal thorax was scored at 6 weeks. One hundred per cent oxygen gave enhancement (dose enhancement factor (DEF) = 1.2), 9 per cent oxygen reduced damage (DEF less than 0.7) and WR 2721 gave PF values in excess of 1.4 at all oxygen concentrations used. This showed that the radiation response of hair follicles was more sensitive to WR 2721 or to changes of oxygen than the lung. The results presented indicate a competitive interaction between WR 2721 and oxygen for the same injury site causing a shift in the oxygen K curve to higher oxygen concentrations. The validity of applying functional or survival measurements to assess the extent of pulmonary fibrosis is discussed.
通过测量呼吸频率、致死率、胸腔积液和羟脯氨酸含量，研究了氧气和WR 2721对小鼠肺部早期和晚期辐射损伤的影响。结果表明，低氧对早期放射性肺炎有保护作用，高氧则有增敏作用。当吸入氧气浓度高于正常水平时，WR 2721的保护作用有降低趋势。当以呼吸频率或致死率作为观察指标时，WR 2721对晚期损伤的保护作用（防护因子PF = 1.6 - 1.65）高于早期肺炎（PF = 1.3 - 1.35）。治疗一年后通过测量胸腔积液得到的防护因子与晚期损伤的其他观察指标相似（PF = 1.7）。相比之下，通过测定一年后肺组织羟脯氨酸含量来评估纤维化程度时，WR 2721的防护因子略低。在相同实验中，于6周时对小鼠背部胸部脱毛程度进行评分。吸入100%氧气会增强损伤（剂量增强因子DEF = 1.2），吸入9%氧气会减轻损伤（DEF < 0.7），在所有使用的氧气浓度下，WR 2721的PF值均超过1.4。这表明毛囊的辐射反应比肺部对WR 2721或氧气变化更为敏感。研究结果表明，WR 2721和氧气在同一损伤部位存在竞争性相互作用，导致氧效应曲线向更高氧浓度偏移。文中还讨论了应用功能或生存指标评估肺纤维化程度的有效性。
