Priest, N. D., Hoel, D. G. and Brooks, P. N. Relative Toxicity of Chronic Irradiation by 45Ca β Particles and 242Cm α Particles with Respect to the Production of Lung Tumors in CBA/Ca Mice. Radiat. Res. 166, 782–793 (2006).
Approximately 1800 female CBA/Ca mice were exposed by inhalation at three dose levels to β particles from 45Ca-labeled fused aluminosilicate particles (FAP), to α particles from 242Cm-labeled FAP, or to carrier control FAP. Another group of mice inhaled no FAP and were designated as untreated cage controls. The FAP in combination with these radionuclides was used to achieve the same spatial and temporal distribution of α- and β-particle dose within the irradiated mice. Some mice were killed to determine the clearance of radiolabeled FAP from their lungs, and the remainder were allocated to a life-span study. All animals were subjected to a detailed necropsy. To facilitate the identification of small tumors, the lungs were rendered transparent in methyl salicylate and examined under back illumination for the presence of lesions. Lung nodules and other microscopic lesions were excised for histological examination. The median survival of mice in all groups was approximately 910 days. The control animals lived longer than those that were irradiated, but it was difficult to determine a dose–response relationship for survival among the exposed mice. Benign adenomas and, less frequently, malignant adenocarcinomas were identified in all animal groups. The prevalence of these tumors was ∼28.8% in the control mice, which is consistent with the results of other studies using the same strain of mouse. After exposure to radionuclide-labeled FAP, there was a significant dose-related increase in the prevalence of lung tumors in 242Cm- (peak prevalence 55%) and 45Ca-exposed (peak prevalence 48.6%) mice. The prevalence of tumors in the mice that received 242Cm-labeled FAP was approximately twice that in the mice that inhaled 45Ca-labeled FAP within the range of doses employed (0.55–4.69 Gy). Using the ratio of the slope of the linear component of the dose–response curves, the toxicity of the α particles relative to the β particles was 1.5 (90% CI: 0.7, 9.0) for all adenomas and 9.4 (90% CI: 5.0, 23.0) for the less frequent adenocarcinomas. The relative toxicity for adenocarcinomas was found to decrease with increasing dose.