Abstract One of the central assumptions of modern radiation biology is, that irrespective of the radiation sort, DNA double strand breaks are induced in direct proportion to radiation dose. However, recent studies of DNA replication have led to the proposal that a local unwinding of the DNA helix occurs in the replication initiation region. Thus, it can be expected that during the DNA replication phase the induction of DNA double strand breaks would contain a quadratic dose component as the consequence of two independently induced single strand breaks. Indeed, the quadratic component does have a maximum value in the DNA replication phase. This process has important implications for radiation biology in general, and the measurement of DNA double strand breaks as a function of dose, in particular.