Transposable genetic elements, spontaneous mutations and the doubling-dose method of radiation genetic risk evaluation in man

The principal aspects of the 'doubling-dose method' for the evaluation of genetic radiation hazards in man are briefly reviewed. With this method, the expected increase in risk from radiation is expressed as a fraction of the current prevalence of these disorders, and thus in relation to an understandable frame of reference. Since the doubling dose is estimated as a ratio of spontaneous to induction rates of mutations, its magnitude is susceptible to changes in either the numerator or the denominator. Studies have demonstrated the existence of mobile DNA sequences in the genome and their causal role in the origin of spontaneous mutations. If a major proportion of spontaneous mutations in man is mediated by these mobile DNA sequences, and if their mobility is unaltered by radiation exposures, the calculation of the doubling dose in the manner mentioned above, and its use in risk evaluations becomes questionable. However, considerations based on the organization of the human genome would suggest that it is unlikely that a major fraction of spontaneous mutations that lead to disease states in man is due to mobile genetic elements. Consequently, the use of the doubling-dose method for the evaluation of genetic radiation hazards in man would appear to be valid at the present time. (Auth.)