exposure, play an important role in the development of lung-cancer, at least in experimental animals (Cross 1994a,b).

INTERACTIONS BETWEEN LUNG CARCINOGENS

Radon is only one of the respiratory carcinogens to which humans are exposed. Tobacco-smoking is an extremely important risk factor for lung-cancer in miners, as well as in the general population; and other lung carcinogens, such as arsenic, are also present in mines. A brief review of the in vitro and in vivo studies related to the issue of interactions between lung carcinogens follows.

Using an in vitro assay for oncogenic transforming C3H10T1/2 cells, Piao and Hei (1993) applied cigarette-smoke condensate (CSC) and observed a dose-dependent increase in the incidence of both cytotoxicity and oncogenic transformation. The frequency was significantly increased if the CSC was combined with a dose of either gamma rays or alpha particles. The transformation frequencies in cells treated with a combination of CSC and 0.5 Gy of alpha particles with energies selected to simulate radon-progeny alpha particles was consistent with the 2 agents acting in an additive manner, not a multiplicative manner.

The report of the BEIR IV committee (NRC 1988) reviewed the animal studies that included exposure to both radon progeny and cigarette smoke. The relevant studies included experiments involving rats conducted by the Compagnie Generale des Matieres Nucleaires (COGEMA) in France and experiments involving dogs conducted by Pacific Northwest Laboratories (PNL) in the United States. The report noted that the COGEMA experiments showed synergism (greater-than-additive effects) if the exposure to cigarette smoke followed the exposure to radon progeny but not if the smoke exposure preceded the radon-progeny exposure. In the PNL experiments, lung tumor incidence was decreased if the animals were exposed to radon progeny and cigarette smoke on the same day, as opposed to sequentially.

Since the BEIR IV report, there have been several additional reports from COGEMA (Monchaux and others 1994) and PNL (Cross 1992). Cross and coworkers have reviewed the newer studies (Cross 1992, 1994a,b). The PNL group conducted initiation-promotion-initiation experiments with cigarette smoke and radon exposure (Cross 1992). Those experiments involved various sequences of exposure to smoking and radon progeny and splitting the dose of radon progeny. Only preliminary findings on lung tumors are available and the number of cancers has been very small. The findings of the COGEMA studies have been summarized recently (Monchaux and others 1994; Yao and others 1994). The extent to which lung-cancer incidence was increased by cigarette-smoke exposure after radon exposure was shown to depend on the duration of exposure to smoke. Decreasing duration was associated with decreasing lung-cancer incidence.

In spite of long-term research by 2 groups of investigators, the animal ex-



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement