Jones C W, Mays C W, Taylor G N, Lloyd R D, Packer S M
Radiat Res. 1986 Sep;107(3):296-306.
Groups of adult female C57BL/Do mice were injected intraperitoneally with graded activities of monomeric 239Pu(IV) citrate at 10 weeks of age. Beginning 3 days after plutonium injection, some mice received repeated subcutaneous injections of Zn Na3 diethylenetriaminepentaacetate (Zn-DTPA). Each injection was 37 mumol Zn-DTPA/kg body weight. To evaluate protection from bone sarcoma, brief, intermediate, or protracted chelation therapies were administered to groups of mice. The brief chelation therapy covered a 2-week period, the intermediate therapy 2 months, and the protracted therapy 1 year. The mice were followed throughout life and examined for bone sarcoma. Both skeletal dose and bone sarcoma risk were reduced by chelation. The bone sarcoma incidences in the mice given chelation treatments generally fell below the dose-response curve for the mice not given DTPA, indicating that the cancer risk was reduced more than that corresponding to the decreased skeletal dose. This results suggests that Zn-DTPA preferentially removed Pu from the most carcinogenic locations in the skeleton, such as on bone surfaces near living cells.
成年雌性C57BL/Do小鼠在10周龄时腹腔注射不同活度的柠檬酸钚(IV)单体。钚注射3天后,部分小鼠皮下重复注射二乙烯三胺五乙酸锌钠(Zn-DTPA),每次注射剂量为37 μmol Zn-DTPA/kg体重。为评估对骨肉瘤的防护效果,对几组小鼠进行了短期、中期或长期螯合治疗。短期螯合治疗为期2周,中期治疗为期2个月,长期治疗为期1年。对小鼠进行终生跟踪并检查骨肉瘤情况。螯合治疗降低了骨骼剂量和骨肉瘤风险。接受螯合治疗的小鼠骨肉瘤发病率通常低于未给予二乙三胺五乙酸(DTPA)的小鼠的剂量反应曲线,这表明癌症风险的降低幅度超过了与骨骼剂量降低相对应的幅度。这一结果表明,Zn-DTPA优先从骨骼中最具致癌性的部位去除钚,比如靠近活细胞的骨表面。