Risk of fatal versus incidental lung cancer in radon-exposed rats: A reanalysis of French data

This review summarizes data on lung cancer risk from radon experimental studies performed by our group in France with emphasis on the most recent findings and analyses on the influence of dose-rate and that of fatal versus incidental tumors. A dose-effect relationship was established in rats, which was very similar for medium and high cumulative exposures, to that observed in uranium miners. At low cumulative exposures in the range of 0.18 Jhm -3 (50 WLM) to 0.36 Jhm-3 (100 WLM), the proportion of fatal lung cancer is about 80% that of total lung cancers. In contrast, at cumulative exposures of 0.72 Jhm-3 (200 WLM) and higher, the proportion of fatal lung cancer is about half that of total lung cancers. The parameters that influence fatal lung cancer risk are cumulative exposure, potential alpha energy concentration (PAEC), exposure rate, and protraction of exposure. At high cumulative exposures up to 10.8 Jhm-3 (3,000 WLM), an inverse dose-rate effect similar to that observed in uranium miners was also found in rats. The inverse exposure-rate effect was observed mainly at the highest exposure-rates. In contrast, our recent results indicate that at relatively low cumulative exposures of 0.36 Jhm-3 (100 WLM), comparable to lifetime exposures in high-radon houses or current underground mining exposures, the risk of lung cancer in rats decreases with decreasing PAEC, i e., exposure rate. These data suggest that the induction of lung cancer results from a complex inter-play between cumulative exposure and exposure rate, with an optimal combination of these two parameters that results in a maximum risk of lung cancer induction. They support the hypothesis that, at low doses, the risk of lung cancer is governed by the rate at which the dose is delivered, and not by the total cumulative dose alone. These data are also consistent with those of underground uranium miners showing an inverse dose-rate effect at high cumulative exposures, but an attenuation of this effect at cumulative exposures lower than 0.18 Jhm-3 (50 WLM). They support both an inverse dose-rate effect at high cumulative exposures, as well as its attenuation or disappearance at low cumulative exposures