An illustrative comparison of the event-size distributions for gamma-rays and alpha -particles in the whole mammalian cell nucleus

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Abstract
Recent laboratory studies of endpoints designated as due to radiation-induced genomic instability have cast doubt on the validity of the current theoretical framework. Under this framework extrapolations are made from directly determined risks of radiation-induced cancer to those circumstances for which no direct information exists, namely at low doses and dose rates at low LET and at low dose exposures to high LET radiations. Based upon an approach in which the 'state' of the genome, as exemplified by the pattern of gene expression, rather than the base sequence of the genomic DNA, is taken to be the origin of genomic stability, it is hypothesized that the critical factor determining the likelihood of destabilization by ionizing radiation is the dose to the whole cell nucleus. The frequency distributions of event sizes from two qualities of radiation, low LET y-rays and 5 MeV alpha-particles, are compared with 60Co gamma-rays being taken to be a low LET reference radiation in determining the RBE of other radiation qualities. In the absence of measured event-size distributions for 60Co gamma-rays in spheres of similar size to the human cell nucleus, the 4.5 microm sphere has been chosen as illustrative. Frequency distributions for 5 MeV alpha-particles are derived, based on the idealized situation of a parallel beam of constant LET, with all particles traversing the sphere. When compared for a dose of 1 mGy the event-size (dose) distributions of the two qualities do not intersect. It is estimated that only 0.4% of the energy from the alpha-particles falls in the range of event sizes that can be produced by 60Co gamma-rays. Contrary to belief over the past 50 years, there is, in this low dose range, no 'continuum' based upon quantities such as LET or lineal energy that would provide a basis for extrapolation from measured RBE values. RBE is thus seen to be purely empirical. In addition, the potential to induce effects in bystander cells is not considered when deriving weighting factors for alpha-particles of the type that contribute significantly to public exposure to environmental radiation.

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