Oxygen-dependent protection of radiation lung damage in mice by WR 2721.

Oxygen-dependent protection of radiation lung damage in mice by WR 2721.
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WR 2721 对小鼠放射性肺损伤的氧依赖性保护。

DOI:
10.1080/09553008414551791
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发表时间:
1984
期刊:
International journal of radiation biology and related studies in physics, chemistry, and medicine
影响因子:
--
通讯作者:
Steel,GG
Steel,GG
中科院分区:
--
文献类型:
--
作者:
Down,JD;Laurent,GJ;McAnulty,RJ;Steel,GG

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本文通过测定呼吸频率、死亡率、胸水和羟脯氨酸含量,研究了氧和WR-2721对小鼠早期和晚期放射性肺损伤的改善作用。低氧对早期放射性肺炎有保护作用,而高氧对早期放射性肺炎有增敏作用。WR 2721的保护作用有随着呼吸氧浓度升高到正常水平以上而降低的趋势。当使用呼吸频率或致死率时,WR 2721对晚期损伤的保护(PF = 1.6 - 1.65)高于早期肺炎(PF = 1.3 - 1.35)。治疗后1年测量胸水获得的保护因子(PF)与其他晚期损害终点的保护因子(PF = 1·7)相似。相比之下,通过测定1年时肺羟脯氨酸的纤维化测量值得出WR 2721的保护因子略低。在相同的实验中,在6周时对背侧胸部的脱毛程度进行评分。100%的氧气可增强(剂量增强因子(DEF)= 1.2),9%的氧气可降低损伤(DEF <0.7),WR 2721在所有氧气浓度下的PF值均超过1.4。这表明毛囊对WR 2721或氧变化的辐射反应比肺更敏感。结果表明,WR 2721和氧之间的竞争性相互作用,对同一损伤部位造成的位移在oxygenK曲线,以更高的氧浓度。应用功能或生存测量的有效性,以评估肺纤维化的程度进行了讨论。
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 determinations 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 < 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 oxygenKcurve to higher oxygen concentrations. The validity of applying functional or survival measurements to assess the extent of pulmonary fibrosis is discussed.