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

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 k 169 WL), uranium ore dust (at 12.9 5 6.7 mglm') 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. tract lesions. However, exposure to 20 cigarettedd, 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 ore 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. 50mo of exposure, might partially account for the absence of tumors in experiments where exposures terminated before 50 mo.

Mortality of a cohort of French uranium miners exposed to relatively low radon concentrations

“…Studies of miners in mines other than uranium have also demonstrated the role of radon in bronchogenic cancer (Lubin et al, 1990;Radford & St. Clair Renard 1984;Morrison et al, 1988). The results of these epidemiological studies and of certain animal studies (Cross et al, 1982;Chameaud et al, 1985) led the International Agency for Research on Cancer (IARC) in 1987 to include radon in the list of carcinogenic substances in humans (IARC vol. 43).…”

Cigarette Mainstream Smoke: The Evolution of Methods and Devices for Generation, Exposure and Collection

“…After habituation dogs tolerated as many as 20 cigarettes in an 8 hour period. This equipment was employed by CROSS et al (385) in a study, which examined the effect of chronic cigarette smoke exposure on pulmonary lesions in beagle dogs. An ancillary observation revealed that about 30% of inhaled TPM from cigarettes spiked with 14 C-dotriacontane-16,17 was deposited in the lungs of two (sacrificed) dogs.…”

Review Article: A Review of Chronic Inhalation Studies with Mainstream Cigarette Smoke, in Hamsters, Dogs, and Nonhuman Primates

“…Some of the more complete studies used radiolabelled markers such as 14 C-dotriacontane, providing de nitive data on the amounts of smoke deposited in the lungs of the experimental animals (13,28).…”