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不同年龄比格犬注射137CsCl后的生物学效应。

Biological effects of 137CsCl injected in beagle dogs of different ages.

作者信息

Nikula K J, Muggenburg B A, Griffith W C, Carlton W W, Fritz T E, Boecker B B

机构信息

Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185, USA.

出版信息

Radiat Res. 1996 Nov;146(5):536-47.

PMID:8896580
Abstract

The toxicity of 137Cs in the beagle dog was investigated at the Inhalation Toxicology Research Institute (ITRI) and Argonne National Laboratory (ANL) as part of programs to evaluate the biological effects of both radionuclides in atomic bomb fallout and internally deposited fission-product radionuclides. In the ITRI study, young adult dogs were exposed once by intravenous injection to a range of 137Cs concentrations; the results have recently been published (Nikula et al., Radiat. Res. 142, 347-361, 1995). The purpose of the present report is to summarize the ANL study and to compare the results of the two studies. At ANL, 63 dogs in three age groups (15 juveniles, 142-151 days old; 38 young adults, 388-427 days old; and 10 middle-aged dogs, 1387-2060 days old) were given 137Cs intravenously at levels (61-162 MBq/kg) near those expected to be lethal within 30 days after injection. There were 17 control dogs from the same colony. Twenty-three of the dogs injected with 137Cs, including all middle-aged dogs, died within 52 days after injection due to hematopoietic cell damage resulting in severe pancytopenia that led to fatal hemorrhage and/or septicemia. The other significant early effect was damage to the germinal epithelium of the seminiferous tubules of all male dogs. These early effects are the same as those reported for the dogs injected with 137Cs at ITRI. In addition, the design of the ANL study revealed an age- and gender-related differential radiosensitivity for early effects: The middle-aged dogs died significantly earlier due to complications of hematological dyscrasia compared to the juvenile and young adult dogs, and the middle-aged females died significantly earlier than the middle-aged males. The most significant non-neoplastic late effects in the 137Cs-injected dogs from ANL and ITRI were atrophy of the germinal epithelium of seminiferous tubules with azoospermia, and a significant dose-dependent decrease in survival. However, the survival of the ANL dogs was decreased more than that of the ITRI dogs at similar radiation doses from 137Cs. Numerous neoplasms occurred at many different sites in the dogs injected with 137Cs at ANL and ITRI. Two differences in the findings of the two studies were that (1) there was an increased risk for malignant thyroid neoplasms in the ANL male dogs injected with 137Cs, but not the ITRI dogs of either gender, and (2) there was an increased relative risk for benign neoplasms excluding mammary neoplasms in the ITRI dogs injected with 137Cs, but not the ANL dogs. In both groups, there were dose-related increased incidences of malignant neoplasms, malignant neoplasms excluding mammary neoplasms, all sarcomas considered as a group, all non-mammary carcinomas considered as a group and malignant liver neoplasms. In summary, the similarity of the findings between the two studies and the dose-response relationships for survival and for large groupings of neoplasms suggests that these results are consistent findings in 137Cs-injected dogs and might be dose-related late effects in humans exposed to sufficient amounts of internally deposited 137Cs.

摘要

作为评估原子弹落尘中放射性核素和体内沉积裂变产物放射性核素生物学效应项目的一部分,吸入毒理学研究所(ITRI)和阿贡国家实验室(ANL)对137Cs在比格犬中的毒性进行了研究。在ITRI的研究中,成年幼犬通过静脉注射一次性暴露于一系列137Cs浓度下;其结果最近已发表(Nikula等人,《辐射研究》142, 347 - 361, 1995)。本报告的目的是总结ANL的研究并比较两项研究的结果。在ANL,三个年龄组的63只犬(15只幼犬,142 - 151日龄;38只成年犬,388 - 427日龄;10只中年犬,1387 - 2060日龄)通过静脉注射给予137Cs,剂量(61 - 162 MBq/kg)接近预计注射后30天内致死的剂量。有17只来自同一犬群的对照犬。23只注射了137Cs的犬,包括所有中年犬,在注射后52天内死亡,原因是造血细胞损伤导致严重全血细胞减少,进而引发致命性出血和/或败血症。另一个显著的早期效应是所有雄性犬的生精小管生精上皮受损。这些早期效应与ITRI报告中注射137Cs的犬的情况相同。此外,ANL研究的设计揭示了早期效应存在年龄和性别相关的放射敏感性差异:与幼犬和成年犬相比,中年犬因血液系统发育异常并发症死亡明显更早,且中年雌性犬比中年雄性犬死亡明显更早。ANL和ITRI注射过137Cs的犬中最显著的非肿瘤性晚期效应是生精小管生精上皮萎缩伴无精子症,以及生存率显著的剂量依赖性下降。然而,在相似的137Cs辐射剂量下,ANL犬的生存率下降幅度比ITRI犬更大。在ANL和ITRI注射137Cs的犬中,许多不同部位都出现了大量肿瘤。两项研究结果的两个差异在于:(1)ANL注射137Cs的雄性犬患恶性甲状腺肿瘤的风险增加,但ITRI的任何性别犬均未出现这种情况;(2)ITRI注射137Cs的犬患除乳腺肿瘤外的良性肿瘤的相对风险增加,但ANL的犬未出现这种情况。在两组中,恶性肿瘤、除乳腺肿瘤外的恶性肿瘤、所有肉瘤作为一组、所有非乳腺癌作为一组以及恶性肝肿瘤的发病率均与剂量相关增加。总之,两项研究结果的相似性以及生存率和大量肿瘤分组的剂量 - 反应关系表明,这些结果是注射137Cs犬的一致发现,可能是暴露于足够量体内沉积137Cs的人类的剂量相关晚期效应。

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