Carcinogenic Effects of Radon Daughters, Uranium Ore Dust and Cigarette Smoke in Beagle Dogs

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Abstract
The development of pulmonary lesions in beagle dogs was studied following chronic inhalation exposures to radon (at 105 ± 20 nCi/l), radon daughters (at 605 ± 169 WL), uranium ore dust (at 12.9 ± 6.7 mg/m3) and cigarette smoke. Chronic exposures to mixtures of these agents caused significant lifespan shortening when compared with controls. Survival times of controls and smoke-exposed dogs were equivalent during the 4 to 5-yr mean survival time of the dogs exposed to radon-daughter and ore-dust mixtures (with or without added cigarette smoke). Animals with tumors of the respiratory tract generally had cumulative radon-daughter exposures exceeding 13,000 WLM, and their survival time was longer than the survival time of nontumor-bearing animals. Under the conditions of the experiment, exposure to cigarette smoke was found to have a mitigating effect on radon daughter-induced tumors. It is uncertain whether this would be a general finding applicable to other levels of exposure to radon daughters, uranium ore dust and cigarette smoke. Exposures to smoke from 10 cigarettes/d, 7 d/wk produced no significant respiratory tract lesions. However, exposure to 20 cigarettes/d, 7 d/wk resulted in pulmonary emphysema, fibrosis and chronic bronchitis and bronchiolitis. Emphysema and fibrosis were much more prevalent and severe in the dogs exposed to mixtures which included radon daughters and uranium are dust. These dogs also had adenomatous lesions which progressed to squamous metaplasia of aleveolar epithelium, epidermoid carcinoma and bronchioloalveolar carcinoma. Pathologic changes in the airways of these dogs were most prominent in the nasal mucosa, and included a few squamous carcinomas in the nasal cavity. We conclude that the beagle dog is a useful animal for modeling pulmonary lesions produced by uranium mine air contaminants. Tumors were produced at levels that did not greatly exceed some exposures reported for uranium miners. These tumors, found after approx. 50 mo of exposure, might partially account for the absence of tumors in experiments where exposures terminated before 50 mo.

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