Effects of Radiation Quality on the Induction of Leukaemia in CBA/CA Mice

Purpose: To study the induction of myeloid leukaemias in mice following the administration of fused aluminosilicate particles (FAP) incorporating aloha- and beta-emitting radionuclides. This information will be used to estimate the most appropriate value for the quality factor of high LET radiations with respect to radiation-induced haemopoietic malignancies.

Status: 1991 - 1995

Treatment: Single intravenous administration of fused aluminosilicate particles (FAP) labelled with Cm-242 (alpha-emitter) or Ca-45 (beta-emitter). Actual diameter of FAP =1.90 ± 0.85 μm.

Dosimetry: Radiochemical analysis to determine Cm-242 or Ca-45 content of tissues from mice killed at 1, 7, 14, 30, 76, 150, 300 and 601 days post injection. Trapezoidal method used to calculate average radiation dose to tissues. Also autoradiographic analysis of liver, spleen and bone marrow to determine microdistribution of FAP.

Endpoints: Life-span study with sacrifice of moribund animals. Necropsy observation and histopathology of all macroscopically obvious abnormalities. Also full haematology for all animals killed in extremis

Animal: Female CBA/Ca mice 10 weeks of age (approximately 20 g) at time of exposure

Results: Following injection with the highest levels of Cm-242 or Ca-45 FAPs, survival was reduced by about 4 and 3 months respectively from the 900 days lifespan of controls . Liver tumours were observed in about 10% of the controls but in about 20% of Cm242-injected mice. Subcutaneous masses thought to arise from benign enlargement of subcutaneous lymph nodes were the most common (30%) abnormality in controls and contributed to morbidity and mortality of the animals. However, the incidence of these masses was reduced in animals injected with the highest levels of Cm-242 or Ca-45 FAPs. On the contrary the incidence of animals with enlargement of multiple lymph nodes, splenomegaly and accumulation of fluid in abdomen and thoracic cavity, signs characteristic of leukaemias, increased from low levels in controls to 11% following injection of radio-labelled FAPs. The histopathological evaluation is now under way.

研究目的：探究注射搭载α及β发射性放射性核素的熔融铝硅酸盐颗粒（fused aluminosilicate particles, FAP）后，小鼠髓系白血病的诱导发生情况。本研究结果将用于估算针对辐射诱导造血系统恶性肿瘤的高传能线密度（LET）辐射的品质因数最优取值。
研究周期：1991年—1995年
处理方式：对小鼠单次静脉注射搭载锔-242（Cm-242，α发射体）或钙-45（Ca-45，β发射体）的熔融铝硅酸盐颗粒（FAP）；FAP实际粒径为1.90±0.85 μm。
剂量学分析：分别在注射后1、7、14、30、76、150、300及601天处死小鼠，通过放射化学分析检测其组织内Cm-242或Ca-45的含量；采用梯形法计算组织的平均辐射剂量。同时对肝脏、脾脏及骨髓开展放射自显影分析，以明确FAP的微观分布特征。
观测终点：采用生存期研究方案，对濒死动物实施安乐死。对所有肉眼可见的异常组织进行剖检观察与组织病理学检测；同时对濒死状态下处死的所有动物完成全血细胞学检测。
实验动物：暴露时为10周龄的雌性CBA/Ca小鼠，体质量约20 g。
实验结果：注射最高剂量Cm-242标记FAP或Ca-45标记FAP的小鼠，其生存期相较于对照组（对照组生存期为900天）分别缩短约4个月和3个月。对照组小鼠肝脏肿瘤发生率约为10%，而Cm-242注射组小鼠的肝脏肿瘤发生率约为20%。对照组最常见的异常为皮下肿块（占比30%），该类肿块被认为源于皮下淋巴结的良性增生，是导致动物发病与死亡的主要因素。但在注射最高剂量放射性标记FAP的小鼠中，此类皮下肿块的发生率有所降低。与之相反，表现为多淋巴结肿大、脾脏肿大及腹腔与胸腔积液（白血病典型体征）的动物占比，从对照组的低水平升至放射性标记FAP注射后的11%。目前组织病理学评估工作仍在进行中。