HIGH-INCIDENCE OF MALIGNANT LUNG CARCINOMAS IN RATS AFTER INHALATION OF (PUO2)-PU-239 AEROSOL

Female Wistar strain rats were exposed to a single inhalation of a sub micron-size aerosol of high-fired (PuO2)-Pu-239 to investigate pulmona ry carcinogenesis during lifespan periods. The absorbed lung doses of the exposed anmals ranged from 0.6 to 12 Gy and were well correlated w ith the initial lung deposition (ILD) of 0.1 to 2.3 kBq. Survival and induction of primary lung tumors in 116 exposed rats were compared wit h those in 56 untreated control rats in respect to lung doses received . Mean survival time was greatly reduced, and the cumulative incidence of total lung tumors was markedly increased to 90-100% in rats that r eceived more than 4 Gy, whereas of the controls only one animal (1.8%) died of primary lung tumors. Primary but benign adenomas were present in exposed animals given 1.0 Gy or less, and the incidence of adenoma s was 22-25% at 4-5 Gy, but decreased sharply to 3-5% at 6-8 Gy. In co ntrast, no malignant carcinomas, including adenocarcinomas, adenosquam ous carcinomas and squamous cell carcinomas, developed at a dose of le ss than 1.0 Gy, whereas they were present in 75% or more of the rats g iven 4-10 Gy, but only in 55% at 12 Gy. Although there were no clear d ifferences in the dose and time required for induction among the carci noma types, all tended to develope in earlier periods after inhalation than adenomas. Despite the limited number of exposed animals that rec eived lower doses, results suggest that malignant lung carcinomas are highly and early induced and have a different dose-effect relationship than benign adenomas at doses of more than 1 Gy after inhalation expo sure to (PuO2)-Pu-239.