Relative Toxicity of Chronic Irradiation by$^{45}Ca\;\beta$Particles and$^{242}Cm\;\alpha$Particles with Respect to the Production of Lung Tumors in CBA/Ca Mice

• Published in: Radiation research 2006-11, Vol.166 (5), p.782-793
• Main Authors: Priest, N. D., Hoel, D. G., P. N. Brooks
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenoma; Dosage; Dose response relationship; Inhalation; Irradiation; Lungs; Mice; Radionuclides; Tumors
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR0618.1

Approximately 1800 female CBA/Ca mice were exposed by inhalation at three dose levels to β particles from$^{45}Ca-labeled$fused aluminosilicate particles (FAP), to α particles from$^{242}Cm-labeled$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 radio-labeled 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$^{242}Cm$-(peak prevalence 55%) and$^{45}Ca-exposed$(peak prevalence 48.6%) mice. The prevalence of tumors in the mice that received$^{242}Cm-labeled$FAP was approximately twice that in the mice that inhaled$^{45}Ca-labeled$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.