year. For comparison, it requires an exposure of 100 WLM to reach the level at which the average exposure to stem cells reaches one alpha particle per nucleus (Harley and others 1996). Therefore, complex considerations of dose rates and total doses that are important for miners or other people with high occupational exposure are unimportant in consideration of domestic exposure (Brenner and others 1995; Brenner 1992) (see also BEIR VI report National Research Council 1999).

Alpha particles traverse a cell in less than 10-12 seconds and deposit energy corresponding to about 10–50 cGy (Jostes 1996). As the particles slow down, they deposit increasing amounts of energy (linear energy transfer, or LET) per unit length of track, reaching a maximum at the end of their track at what is known as the Bragg peak. The relative biologic effectiveness (RBE) of an alpha particle is therefore variable along its track according to whether the LET reaches a maximum at the Bragg peak (Brenner and others 1995). The average track through a spherical cell nucleus can cross many individual strands of DNA, depositing energy in the form of clusters of ionizations, and produce corresponding numbers of double-strand breaks. These breaks have a complex chemistry and have been described as multiply locally damaged sites (MLDSs) (Ward 1990). Because of the track structure and the tightly coiled nature of DNA in the nucleus, there is likely to be a nonuniform distribution of DNA breaks with an excess of small fragments which might get lost or incorrectly positioned in the process of rejoining (Ritter and others 1977).

Ion clusters can also produce reactive oxygen intermediates which can damage individual DNA bases, and at high doses, alter intracellular signal transduction, reduce macromolecular synthesis, and trigger processes that resemble those from inflammatory cytokines involved in other kinds of tissue injury. A series of early experiments in the 1950 and 1960s used collimated beams of alpha particles and other kinds of radiation and demonstrated the relative importance of nuclear, cytoplasmic, and extracellular irradiation (Munro 1970b; 1970a; Smith 1964). Those experiments showed that nuclear damage was potentially lethal; nonnuclear damage could also produce detectable effects, such as reduced DNA synthesis, but it was not lethal. Extracellular damage involved reactive oxygen intermediates that could be prevented by catalase (which degrades hydrogen peroxide) (Dendy and others 1967). More recent and technically sophisticated experiments in which the effects of single alpha particles can be estimated or observed have resulted in essentially similar conclusions (Hei and others 1997; Hickman and others 1994).

Lethality of Alpha-Particle Tracks Through Cells and Tissues

The dose required to produce an average of one lethal hit to a cell (the D37) corresponds to about 1.2–1.5 alpha particles per spherical nucleus (Jostes 1996). Flattened cells can withstand more tracks (up to 15 or even more), each of



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