plutonium-dioxide and Carcinoma

Radiation-induced pulmonary carcinogenesis was compared in female Wistar rats following either inhalation exposure to alpha-emitting (239)PuO(2) aerosols, whole-body or thoracic X-ray irradiation. Dose-dependent survival reduction was correlated with increased malignant lung tumors at doses over 0.45 Gy, reaching the maximum incidence of 90% at 6.6-8.5 Gy in (239)Pu-exposed rats. While the differential dose responses for each histopathological type of tumors were noted, almost 70-80% were carcinomas among all of the primary tumors from (239)Pu-exposed rats. As the dose response curves for lung carcinomas were compared, the slope of the fit linear equation and the calculated relative effectiveness for 50% incidence of lung carcinomas were approximately 11-times as high in (239)Pu-exposure as those of thoracic X-irradiation. The numbers of tumor lesions distributed in the lung per tumor-bearing animal were about 2-fold more in (239)Pu-exposed rats, while the proportions of their histopathological types were similar between (239)Pu-exposure and X-irradiation. These results indicate that the magnitudes of the relative effectiveness or risk for pulmonary carcinogenesis are greater in (239)Pu-exposure than X-irradiation, and that radiation-induced lung tumors appear to originate mostly from the same target epithelial cells.

Topics: Adenoma; Animals; Carcinoma; Computer Simulation; Dose-Response Relationship, Radiation; Female; Inhalation Exposure; Lung Neoplasms; Models, Biological; Neoplasms, Radiation-Induced; Plutonium; Radiation Dosage; Radiometry; Rats; Survival Rate; Whole-Body Irradiation; X-Rays

Pulmonary carcinogenesis was compared in female F344 and Wistar rats after inhalation of high-fired 239PuO2. Plutonium particle aggregation, as determined by quantitative light and scanning electron microscopic autoradiography, was greater for the F344 strain than for the Wistar strain. The median survival times were similar in control and low-dose (0.8-1.0 Gy) groups of both strains, but were significantly decreased in the high-dose (34-37 Gy) groups of both strains. Squamous metaplasia was not found in control or low-dose groups of either strain, but was found in 62-65% of high-dose groups of both strains. Adenomatous metaplasia was considerably higher in control and low-dose groups of F344 rats than in Wistar rats. A total of 87 lung tumors were found in 140 exposed F344 rats and 46 lung tumors in 176 exposed Wistar rats. The incidence of lung tumors in F344 rats was 1.7% in controls, 20% in the low-dose group and 82% in the high-dose group. The incidence of lung tumors in Wistar rats was 0.1% in controls, nil in the low-dose group and 68% in the high-dose group. About half of all lung tumors in both strains were considered to be the primary cause of death. The median survival times of rats of both strains in the high-dose groups that died with lung tumors were greater compared with rats in these groups that died without lung tumors. In contrast, these differences did not occur among rats in the low-dose groups. The absolute risk was 1900 lung tumors per 10(4) Rat-Gy for F344 rats receiving low doses and nil for Wistar rats receiving low doses, but about 210 lung tumors per 10(4) Rat-Gy for high-dose groups of both strains. The adenomatous tumor phenotype predominated in the F344 strain, while the squamous tumor phenotype predominated in the Wistar strain. Risk of squamous tumors was similar for both strains. Overall, the F344 strain appears to be more "sensitive" than the Wistar strain to formation of lung tumors at low to moderate doses from inhaled 239PuO2 due mostly to an increased incidence of adenomatous phenotype tumors.

Topics: Aerosols; Animals; Carcinoma; Dose-Response Relationship, Radiation; Epithelium; Female; Lung Neoplasms; Neoplasms, Radiation-Induced; Plutonium; Rats; Rats, Inbred F344; Rats, Wistar; Sarcoma, Experimental