DIFFERENTIAL DOSE RESPONSES OF PULMONARY TUMOR TYPES IN THE RAT AFTERINHALATION OF PLUTONIUM DIOXIDE AEROSOLS

Dose responses were compared among primary lung tumors and their histo logical types induced by a single inhalation exposure of female Wistar strain rats to submicron-size and polydispersed aerosols of plutonium dioxide ((PuO2)-Pu-239). While the primary lung tumors were found onl y in 2.3% of the unexposed control animals, the frequency of all the p rimary lung tumors in the exposed animals was 44% at the mean lung dos e of 0.71 Gy, and increased sharply at the doses of 1.5 Gy or more, re aching the maximum of 97% at 5.4 Gy, and the dose responses around at 1.0 Gy were different between benign and malignant lung tumors. Almost all the pulmonary tumors in the exposed animals were classified into epithelial types such as adenomas, adenocarcinomas, adenosquamous carc inomas. and squamous cell carcinomas. The dose responses were differen t between these tumor types as shown by the peak incidence of adenomas at 0.71 Gy, adenocarcinomas at 2.9 Gy, adenosquamous and squamous cel l carcinomas at 5.4-8.5 Gy, respectively. As the magnitudes of neoplas tic lesions in pulmonary carcinomas were expressed by histological sco res, metaplasias and adenomatous lesions most frequently appeared at d oses of 1.5 Gy, while the appearance and increase of carcinomatous les ions differed in the dose ranges as shown by the peak incidence of ade nocarcinomatous lesions at 2.9 Gy, and adenosquamous or squamous lesio ns at 5.4-6.6 Gy. These results indicate a differential dose response of pulmonary carcinogenesis in which metaplasias and benign adenomas w ere induced at lower doses (< 1.0 Gy), whereas malignant carcinomas we re induced at relatively higher doses (> 1.5 Gy). Together with the in crease of carcinomatous lesions at higher doses, the intranuclear p53 protein accumulation was detectable, but only in a few percentages of malignant carcinomas.