Abstract
Pulmonary carcinogenesis in the rat from a variety of agents may not represent a clear stochastic effect but a threshold response. Both weakly genotoxic quartz and highly genotoxic, α-emitting 239PuO2 induce carcinomas in the lungs of rats. The pathogenesis of pulmonary carcinoma was similar for quartz and plutonium. In both cases, pulmonary carcinogenesis may be explained on the basis of type I alveolar epithelial cell cytotoxicity and type II alveolar epithelial cell proliferative repair. Pulmonary carcinomas are derived from focal regions of particle aggregation in the lung parenchyma, with a gradual evolution of focal inflammation, fibrosis, type II cell hyperplasia, alveolar bronchiolarization, cuboidal and squamous metaplasia, and finally, carcinoma formation. Small doses of particles are insufficient to cause proliferative repair and therefore do not induce carcinomas. Twelve of 53 rats (22.6%) exposed to quartz dust developed pulmonary carcinomas (10 squamous carcinomas and 2 adenocarcinomas). In comparison, the incidence of lung pulmonary carcinomas was 0.095 percent in 1052 sham-exposed control rats (one adenocarcinoma), nil in 1877 rats with lung doses <1 Gy, and 34.2 percent in 228 rats with lung doses >1 Gy (22 adenocarcinomas, 49 squamous carcinomas, and 7 adenosquamous carcinomas). We conclude that dose-response relationships for carcinoma formation in the lung of the rat from highly genotoxic plutonium or weakly genotoxic quartz are both best explained by a threshold model.