On the linearity of the dose-effect relationship of DNA double strand breaks

Most radiation biologists believe that DNA double-strand breaks are induced linearly with radiation dose for all types of radiation. Since 1985, with the advent of elution and gel electrophoresis techniques which permit the measurement of DNA double-strand breaks induced in mammalian cells at doses having radiobiological relevance, the true nature of the dose-effect relationship has been brought into some doubt. Many investigators measured curvilinear dose-effect relationships and a few found good correlations between the induction of the DNA double-strand breaks and cell survival. We approach the problem pragmatically by assuming that the induction of DNA double-strand breaks by 125I Auger electron emitters incorporated into the DNA of the cells is a linear function of the number of 125I decays, and by comparing the dose-effect relationship for sparsely ionizing radiation against this standard. The conclusion drawn in that the curvilinear dose-effect relationships and the correlations with survival are real. The problem of why the dose-effect relationship is curvilinear when microdosimetric considerations predict that even for sparsely ionizing radiation energy deposition in and close to the Watson-Crick double helix should give a linear dose-effect relationship remains.