multiple cell traversals occur with significant probabilities, but are unlikely to be important at low exposure levels that correspond to 1 particle or less per cell.
In summary, the weight of evidence from cellular and molecular studies strongly supports the concept of linearity with dose in cellular systems including cell lethality, mutation, or transformation with no threshold for low-dose alpha-particle irradiation but leaves open the possibility of a change in slope or a departure from linearity for cancer induction at higher doses. The overwhelming evidence for the monoclonal origin of most cancers suggests linearity without threshold would also apply to low-dose radon-induced carcinogenesis. This observation emphasizes the desirability of extrapolating to typical indoor exposures from the lowest exposure range that is practical in the miner data set.
Extrapolation from higher to lower radon exposures is also affected by the inverse dose-rate effect (Brenner 1994). In vivo and in vitro experiments have shown an inverse dose-rate effect for alpha-particle irradiation. Specifically, protracting a given total dose (experimentally, at least 0. 10 Gy) of densely ionizing radiation, such as alpha particles, can increase oncogenic transformation in vitro or carcinogenesis in vivo. This dose-rate effect, whatever its underlying mechanism, operates at doses corresponding to multiple particle traversals per cell but is likely to disappear at low doses corresponding to an average of much less than 1 traversal per cell (Figure 2-2). A similar dependence of effect on exposure is clearly evident in the miner data (Figure 2-3).
Extrapolating radon risk from the full miner data to the low-exposure domestic situation involves extrapolating from a situation in which multiple traversals are common to one in which they are rare; consequently, such an extrapolation would be from a situation in which the inverse dose-rate effect might well be important to one in which it is likely to be unimportant. That presents a problem for the committee's risk assessment in that the mechanisms whereby inverse dose-rate effects operate are not yet established, although several mechanisms have been hypothesized. However, given that both experimental evidence and fundamental biophysical evidence suggest that the inverse dose-rate effect should be of little importance below about 0.35 Jhm-3 (100 WLM), these considerations again underline the importance of assessing risks of radon in homes on the basis of miner data corresponding to as low an exposure as possible.
Experiments with a combination of alpha-particle and tobacco-smoke condensate exposure, using oncogenic transformation in vitro as a test assay, show that effects of the 2 agents are consistent with a purely additive interaction (Piao and Hei 1993). With such in vitro systems, large-scale experiments are possible