terms of life shortening, again as a reflection of increased mortality from tumors (Storer and others 1988; Carnes and others 1989; Covelli and others 1989).
In all experimental studies with rodents, it was difficult or impossible to determine excess tumor rates at γ-ray doses substantially less than 1 Gy. For the purpose of risk estimation, it is therefore assumed in this report that the relevant animal experiments with rodents indicate a neutron RBE for solid tumors of 20–50 compared to a reference γ-ray dose of 1 Gy. Experimental evidence suggests lower neutron RBEs for leukemia; in experiments with RFM mice (Ullrich and Preston 1987), an RBE of about 3 was seen versus a γ-ray dose of 0.5 Gy; at lower γ-ray doses, statistical uncertainty did not permit the specification of a neutron RBE.
As previously described, free electrons can be produced by X- and γ-ray interactions with atoms in tissue. These electrons can then interact with the DNA molecule and create damage in the form of strand breaks or damaged bases; these are known as direct effects. Indirect effects can occur after a photon interacts with a water molecule. Water molecules make up 70% of human tissue. Ejection of an electron from a water molecule by an incoming photon produces an ionized water molecule, H2O+. Trapping of the electron by polarizing water molecules produces a so-called hydrated electron, e-aq. When the ionized water molecule collides with another water molecule, it reacts to produce a highly reactive hydroxyl radical, OH•, according to the reaction
Other reactions produce a hydrogen radical (H•), hydrogen peroxide, and water. Thus, these reactions produce three important reactive species—e-aq, H•, and OH•, which have initial relative yields of about 45%, 10%, and 45%, respectively, in the case of γ-radiation. The reactive species can damage DNA, and such damage is termed an indirect effect.
The relatively long-lived (about 10−5 s) OH• radical is believed to be the most effective of the reactive species; as an oxidizing agent, it can extract a hydrogen atom from the deoxyribose component of DNA, creating a DNA radical. Early experiments demonstrated that about 70% of the DNA damage can be prevented by the addition of OH• scavengers (Roots and Okada 1972). Because OH• is so highly reactive, it has been estimated that only the radicals formed within about 3 nm of DNA can react with it (Ward 1994). Although DNA is deemed the most important target for biological damage that leads to health effects, other sites—such as the nuclear membrane, the DNA-membrane complex, and the outer cell membrane—may also be important for some biological effects. Signal transduction from cell membrane phospholipids damaged by free radicals and oxidizing reactions is an important natural process. This is one set of biochemical pathways by which the effects of ionizing radiation may overlap with the effects of endogenous processes, such as macrophage oxidative bursts. These processes may underlie those seen in irradiated cells that have been characterized as “bystander effects” and “adaptation” (see Chapter 2).
Nikjoo and colleagues (1997, 2002) have modeled the probability of electron and OH• radical interaction with DNA. In a 1997 publication, they modeled the spectrum of DNA damage (direct energy deposition and reactions with diffusing OH• radicals) induced by low-energy secondary electrons (0.1–4.5 keV). They note that to extrapolate available epidemiologic and experimental data from high-dose and high-dose-rate studies to the relevant low levels of single isolated tracks, it is essential to develop a more molecular and mechanistic approach based on the amounts, types, and repairability of the early molecular damage that results from the initial physical and chemical processes. Their calculations for secondary electrons show that most (about 66–74%) low-energy electron interactions in DNA “do not lead to damage in the form of strand breaks and when they do occur, they are most frequently single strand breaks” (SSBs). Although the data are complex, SSB percentages in their study range from about 22 to 27% in the electron energy range of 0.1–4.5 keV and double-strand break (DSB) percentages range from about 1.4–2.4% in the same energy range. However, more than 30% of DSBs are of a more complex form; these complex breaks are somewhat analogous to LMDS, but Nikjoo and colleagues do not include base damage in their model. Their calculations also indicate that the DNA damage tends to be along short lengths of DNA: 1–34 base pairs (bp) for 0.3 and 1.5 keV electrons. The authors conclude that the large deletions seen in radiation-induced mutations may have other mechanisms, such as nonhomologous recombination (Nikjoo and others 1997).
In the case of energetic electron interactions with DNA (0.1 eV to 100 keV electrons), Nikjoo and others (2002) estimate that more than 80% of the interactions do not cause damage in the form of DNA SSBs. Of the interactions that do cause strand breaks, the authors calculate that a small percentage (about 0.5–1.4%) produce DSBs. They note, however, that there is still a considerable contribution (>20%) to the DSB yield from complex DSBs in which a simple DSB is accompanied by at least one additional strand break within 10 bp. As in the low-energy study just described, this model does not include any contribution to the yield of strand breaks from damaged bases.
Another recent study suggests that single low-energy electrons can produce DNA SSBs and DSBs at energies below ionization thresholds (Boudaiffa and others 2000). The authors speculate that these breaks are initiated as direct damage by resonant electron attachment to DNA compo-