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

Purpose: Recent laboratory studies of endpoints designated as due to radiat ion-induced genomic instability have cast doubt on the validity of the curr ent theoretical framework. Under this framework extrapolations are made fro m directly determined risks of radiation-induced cancer to those circumstan ces for which no direct information exists, namely at low doses and dose ra tes 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 patt ern of gene expression, rather than the base sequence of the genomic DNA, i s taken to be the origin of genomic stability, it is hypothesized that the critical factor determining the likelihood of destabilization by ionizing r adiation is the dose to the whole cell nucleus. Calculations: The frequency distributions of event sizes from two qualities of radiation, low LET gamma-rays and 5MeV alpha-particles, are compared wi th Co-60 gamma-rays being taken to be a low LET reference radiation in dete rmining the RBE of other radiation qualities. In the absence of measured ev ent-size distributions for Co-60 gamma-rays in spheres of similar size to t he human cell nucleus, the 4.5 mu m sphere has been chosen as illustrative. Frequency distributions for 5MeV alpha-particles are derived, based on the idealized situation of a parallel beam of constant LET, with all particles traversing the sphere. Results: When compared for a dose of 1 mGy the event-size (dose) distributi ons of the two qualities do not intersect. It is estimated that only 0.4% o f the energy from the alpha-particles falls in the range of event sizes tha t can be produced by Co-60 gamma-rays. Conclusions: Contrary to belief over the past 50 years, there is, in this l ow dose range, no 'continuum' based upon quantities such as LET or lineal e nergy that would provide a basis for extrapolation from measured RBE values . RBE is thus seen to be purely empirical. Tn addition, the potential to in duce effects in bystander cells is not considered when deriving weighting f actors for alpha-particles of the type that contribute significantly to pub lic exposure to environmental radiation.