Two-step model for the risk of fatal and incidental lung tumors in rats exposed to radon

Data from 4276 rats with radon exposures up to 10,000 WLM at rates up to 10 00 WL are analyzed with a two-step clonal expansion model. The age dependen ces of the hazard for the risks for fatal and for incidental tumors are ver y different. Therefore, two different parameterizations of the model are us ed in the two cases. In both cases radiation acts only on the initiating mu tation and the clonal expansion, but not on the second mutation. Average ex posure rates of 5 WL for fatal tumors and 0.5 WL for incidental tumors doub le the rate of spontaneous mutations. While the fatal tumors show a linear increase in the effective clonal expansion rate up to about 100 WL average exposure rate and a saturation at higher exposure rates, the incidental tum ors follow a step-like behavior of this parameter. It is proposed that only the fatal lung tumors among the rats be used for generalizations to models for lung cancer in humans. The fitted model for fatal tumors shows an inve rse dose-rate effect at average exposure rates above 20 WL, However, below 10 WL the lung cancer risk per unit exposure decreases with increasing dura tion of exposure. Between 10 and 20 WL, the difference in ERR/WLM between a cute and protracted exposure is small. (C) 1999 by Radiation Research Socie ty.