DAMAGE AND MORBIDITY FROM PNEUMONITIS AFTER IRRADIATION OF PARTIAL VOLUMES OF MOUSE LUNG

DAMAGE AND MORBIDITY FROM PNEUMONITIS AFTER IRRADIATION OF PARTIAL VOLUMES OF MOUSE LUNG
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DOI:
10.1016/0360-3016(94)00660-d
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发表时间:
1995-07-30
影响因子:
7
通讯作者:
TUCKER, SL
TUCKER, SL
中科院分区:
医学1区
文献类型:
--
作者:
LIAO, ZX;TRAVIS, EL;TUCKER, SL

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目的:本研究的目的是:(A)确定照射剂量和体积与小鼠肺损伤和发病率的关系;(B)确定部分肺照射后的发病阈值体积;(C)确定小鼠肺对辐射的反应是否独立于受照区域。采用称重法和CT扫描法测定受照肺体积分数。进行了两个实验,以确定体积效应,并确定小鼠肺对辐射的反应是否均匀。在第一个实验中,单次剂量范围为12~20GyX射线照射的部分体积分别为84%、70%和40%,包括顶端的50%、33%和17%,中间为43%,总和为57%,分别为顶端的17%和底部的40%。在第二次实验中,用12-19.25GY的单次剂量照射50%和70-75%的肺尖和肺底的体积。放射性肺炎的发病率通过两个终点、呼吸频率和12至32周之间的致死率来量化:在照射后。结果:所有剂量照射后,呼吸率和致死率均有明确的剂量-反应曲线。在照射后28周,即肺炎损伤期结束时,呼吸频率和致死率的剂量-反应曲线与全肺照射后的这些数据相比有明显的体积依赖关系向更高的剂量移动。此外,与全肺照射相比,部分肺体积照射的剂量-效应曲线斜率较浅,当照射体积等于或大于参考体积的50%时,呼吸频率的增加与致死率相关。然而,在体积小于40%的照射后,呼吸频率增加并未伴随死亡。在第一次实验中观察到了小鼠肺对辐射的异质性反应,第二次实验证实了这一点。对于给定的照射体积,肺底部的等效剂量总是小于肺尖的等效剂量。当照射体积分别位于肺尖和肺底时,呼吸频率变化的阈值体积分别小于17%和40%。对于致命性,肺底的阈值体积介于40%~70%之间,肺尖大于50%。结论:(A)小鼠肺的体积效应是可消除的,(B)小鼠肺的体积效应表现出明确的发病率阈值,(C)发病率的阈值体积是依赖于终点的,(D)小鼠肺的反应是异质性的,依赖于受照射的部位,对于相同体积的照射,底部照射总是大于顶端照射,(E)组织病理学损伤并不总是产生可观察到的发病率。
Purpose: The aims of this study were to: (a) define the relationship of dose and volume irradiated to damage and morbidity in mouse lung, (b) determine the threshold volume for morbidity after partial lung irradiation; and (c) determine whether the response to radiation of mouse lung is independent of the region irradiated.Methods and Materials: C3Hf/Kam female mice were used in this study. The fractional volume of the lung to be irradiated was determined by two methods, weights and computed tomography (CT) scanning. Two experiments were performed to define the volume effect and to determine whether the response of the mouse lung to radiation was homogeneous. In the first experiment, single doses of x-rays ranging from 12 to 20 Gy were given to partial volumes of 84%, 70%, and 40% including the base, 50%, 33%, and 17% including the apex, to 43% in the middle, and to the sum of 57% as 17% in the apex and 40% in the base. In the second experiment, the same volumes of 50% and 70-75% in the apex and base of the lung were irradiated with single doses ranging from 12-19.25 Gy. Morbidity from radiation pneumonitis was quantitated by two end points, breathing rate and lethality between 12 and 32 weeks: after irradiation. Damage was assessed by histopathological evidence of pneumonitis.Results: Clear well-defined dose-response curves were obtained for both breathing rate and lethality after all volumes irradiated. There was a clear volume-dependent shift of the dose-response curves for breathing rate and lethality at 28 weeks after irradiation, the end of the pneumonitis phase of damage, to higher doses compared with these data after whole-lung irradiation. In addition, the slopes of the dose-response curves for irradiation of partial lung volumes were more shallow compared to those after whole-lung irradiation, Increases in breathing rate correlated with lethality when the volume irradiated was equal to or greater than 50% of the reference volume. However, after irradiation of volumes smaller than 40%, breathing rate increases were not accompanied by death. A heterogeneous response of the mouse lung to radiation was observed in the first experiment and confirmed by the second experiment. For a given volume irradiated, the isoeffect dose was always less for the base than for the apex of the lung. The threshold volume for breathing rate changes was less than 17 and 40% when the irradiated volumes involved the apex and base, respectively, For lethality, the threshold volume was between 40 and 70% for the base and greater than 50% for the apex of the lung. Finally, damage as assessed by histological evidence of pneumonitis was observed in the irradiated area only.Conclusions: (a) The volume effect was resolvable in mice,(b) the volume effect in mouse lung exhibits a clear threshold for morbidity, (c) the threshold volume for morbidity is dependent on the end point, (d) the response of mouse lung is heterogeneous, dependent on the site irradiated, and is always greater for the same volumes irradiated in the base than the apex, and, (e) histopathological damage does not always produce observable morbidity.