Muggenburg B A, Hahn F F, Griffith W C, Lloyd R D, Boecker B B
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA.
Radiat Res. 1996 Aug;146(2):171-86.
A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected 224Ra chloride. The 224Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of 224Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of 224Ra kg-1 body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected 224Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected 224Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed alpha-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of 224Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. The occurrence of bone tumors was highest in the dogs given the highest dose in 50 injections. The age-specific incidence rate for mammary tumors was increased in all three injection groups. The results of this study revealed two important exposure-rate effects. Hematological dyscrasia was amplified by delivery of relatively high doses at a high exposure rate. In contrast, bone tumors were amplified by delivery of relatively high doses at a lower exposure rate (i.e. dose delivered over 1 year rather than 1-3 months). There was a dose-response relationship for the induction of nasal mucosal tumors and mammary tumors. These findings in dogs are similar to those in humans injected with 224Ra, except for the nasal tumors. The calculated risk of developing a bone tumor was about 40 times higher in dogs than reported for humans.
对128只比格犬进行了一项寿命研究，以确定静脉注射氯化镭-224的生物学效应。氯化镭-224的制备方法与用于治疗强直性脊柱炎和结核病的人类静脉注射所用方法相同。因此，从犬类获得的结果可以直接与接受治疗的人类群体进行比较，既有助于阐明暴露率的影响，也便于与缺乏人类数据的其他放射性核素进行比较。使用数量相等的雄性和雌性犬，向其注射四种水平之一的氯化镭-224，使初始体内负荷约为每千克体重13、40、120或350 kBq的氯化镭-224。一组对照犬只注射稀释剂。所有犬只进一步分为三组，分别接受单次注射氯化镭-224（半衰期为3.62天）或稀释剂，或将其平均分为10次或50次每周注射。由于这三种注射方案，注射的氯化镭-224剂量的累积在大约1、3或12个月内分布。每种注射方案包括四种不同的注射水平，导致骨的平均吸收α粒子剂量分别为0.1、0.3、1和3 Gy。观察到的主要早期效应是接受两种最高注射水平之一的犬出现血液恶液质。在接受单次注射氯化镭-224的犬中效应最为严重，导致三只接受最高剂量注射的犬死亡。后期出现的生物学效应是肿瘤。骨肿瘤最为常见，其次是鼻黏膜肿瘤。在50次注射中接受最高剂量的犬中骨肿瘤的发生率最高。所有三个注射组中乳腺肿瘤的年龄特异性发病率均有所增加。本研究结果揭示了两个重要的暴露率效应。血液恶液质在高暴露率下给予相对高剂量时会加剧。相反，骨肿瘤在较低暴露率下给予相对高剂量时会加剧（即剂量在1年内给予而非1 - 3个月内）。鼻黏膜肿瘤和乳腺肿瘤的诱导存在剂量反应关系。犬类的这些发现与注射氯化镭-224的人类相似，但鼻肿瘤除外。计算得出犬发生骨肿瘤的风险比人类报告的约高40倍。
