cussed by various authors (for example, Moolgavkar and others 1993; Crump 1994a,b; Little and others 1994; Moolgavkar 1994; Goddard and Krewski 1995; Little 1995).
Those approaches must be considered desirable, in the long term, as a framework for interpreting the radiation-epidemiologic data. Today, however, it is important to recognize the complexity of the processes involved in radiation carcinogenesis and the many gaps in our knowledge of the most-basic relevant processes. Although the use of biologically-based models provides valuable insights into the carcinogenic process, the models are not sufficiently well developed to be used for quantitative risk estimation; indeed, their use might lend more credibility to the resulting risk estimates than is warranted.
Although all the steps leading from the deposition of radiation energy to the development of cancer are not understood, some general trends have emerged from the considerations in this chapter, which can be used to guide specific assumptions of the epidemiologically based analysis of radon-induced lung-cancer. These trends are discussed in the remaining part of this chapter.
The challenge is to guide the extrapolation of risks from radon-progeny exposures at which effects can readily be observed and risks quantified down to lower exposures at which events might occur with probabilities too small to measure with sufficient precision in any human population. Low exposures and doses correspond to the traversal of cells by single alpha particles. As the dose is further decreased, the insult to cells that are traversed by an alpha particle remains the same, but the number of traversed cells decreases proportionately. There is good evidence that a single alpha particle can cause a substantial change in a cell. For example, a single traversal by an alpha particle with an LET of 120 keV/µm can result typically in about 10–20 double-strand breaks in a cell deduced from measured yields of about 30–40 dsb/Gy for low-LET radiation (Ward 1988; Stenerlow and others 1996), similar relative yields for alpha particles (Jenner and others 1993; Prise 1994), and a dose of about 0.2–0.5 Gy to a cell traversed by a single alpha particle, depending on cellular geometry. Even allowing for the substantial degree of repair that is known to take place, the passage of the particle most likely causes some irreparable damage or permanent change. Direct evidence of such clastogenic changes, based on single alpha-particle microbeam irradiation (Geard and others 1991; Braby 1992; Nelson and others 1996) has been reported. There is also convincing evidence that alpha particles are efficient at inducing genomic instability (Kadhim and others 1992, 1994, 1995; Sabatier and others 1994), so traversal by a single particle can potentially initiate a cascade of events that can lead to chromosomal aberrations or delayed mutations many generations later. The later effects can be in cells adjacent to those actually traversed.