A theory is presented t o explain the effect of radiation on cell survival. The theory is based on the assumption that a double strand break in the DXA helix is the critical damage. The theory is derived from the radiation induced molecular bond breaks in the DNA strands and parameters are included to take account of various repair processes which may occur between the radiation event and the biological result. Implications of the theory with respect to RBE, the oxygen effect and radiological protection are mentioned and a fit of the theoretically derived expression to experimental data for 250 kV, X-rays and 15 MeV neutrons is presented. An appendix contains data which show that the enzymatic repair of single strand breaks in DNA is in accordance with the theoretical analysis of protracted irradiations and that a coherent analysis of the variation of radiation sensitivity in the cell cycle is in strong support of the primary assumption that a double strand break in the DNA helix is the critical damage leading t o cell reproductive death.

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An attempt is made to develop a model for radiation carcinogenesis linking DNA damage to malignancy. A modification of the two-stage model for carcinogenesis developed by Knudson and Moolgavkar (see J. Natl. Acad. Sci. (USA), vol. 68, p. 1037-52, 1981) is combined with a linear-quadratic dose response model for cellular radiation effects to analyse radiation induced lung tumours in rodents for a variety of radiation types and conditions. The combined model provides the possibility of calculating the age dependent and dose dependent incidence of cancer simultaneously and is used to fit data of lung tumours in mice and rats exposed to different radiation types. The satisfactory application of the combined model to animal data has led to an examination of the implications of the model, which may prove to be far-reaching for the extrapolation of risk to low doses, the effect of life exposures and other aspects of radiation risk assessment.

The recombination type of process, which has been proposed by Resnick to explain the rejoining of radiation-induced DNA double-strand breaks, is combined with the molecular theory of radiation action to provide a description of the formation of chromosomal rearrangments. It is shown that the majority of chromosomal aberration types found at the first mitosis after radiation can be explained on the basis of one radiation-induced DNA double-strand break in the backbone of the unineme chromatid, followed by the enzymatically controlled recombinational process for the rejoining of the double-strand break. The recombinogenic process for the repair of DNA double-strand breaks relies on the close association between the broken DNA double helix and homologous DNA. The homologous nature of repeated DNA base pair sequences is used, in this model, to explain the occurrence of chromosomal exchanges between non-homologous chromosomes. The important role which repetitive DNA plays in the formation of chromosomal rearrangements and in the distribution of 'break-points' found in radiation experiments is discussed.

This paper presents a brief argument, based on a mechanistic approach, to show that radiation risk is linear with radiation dose from zero dose up. Similarities in cellular effects lead to the assumption of a common mechanism and the DNA double strand break is identified as the crucial radiation-induced lesion. A cancer model extends the cellular effects to the main radiation risk providing confirmation of the dose effect for cancer at low doses.