Shifting From Dna Centric View Of Radiation Damage In Radiobiology And Its Impact On Low Dose Radioprotection


Ph.D, Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.


A classic experiment of Munro on mammalian cells has clearly shown that the critical targets for radiation induced damages are located in cell nucleus. In the nucleus, DNA has been considered as primary target for radiation induced damage. We now know that ionizing radiation damage DNA directly by direct energy deposition and indirectly via formation of free radicals due to water radiolysis in vicinity of DNA molecules. Damage to a key molecule may be lethal for a cell and has led to the development of target theory of radiation damage. Target theory considers one hit damage for high LET radiation and multi-hit damage for low LET radiation. However, the initial radiation induced DNA damage undergo various repair processes, however un-repaired or mis-repaird DNA damages are converted into mutations, chromosomal aberrations and cell death. Stochastic effects of low dose ionizing radiation for induction of genetic effects and carcinogenesis have been considered as the most important genetic and somatic effects of low dose radiation. It is commonly believed that “any radiation dose, no matter how small, can cause genetic damage and cancer (linear model). However, the last 15 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. Observations of bystander effects in neighboring cells that have not been directly hit have led to suggestions that at low doses these non-targeted effects could contribute to the adverse consequences of low dose radiation exposure. Adaptive response, believed as a beneficial low dose effect and inherent radiosensitivity might also affect linear non-threshold (LNT) concept. Although, it is believed that these radiobiological phenomena affect on LNT model. Radiation protection principles are developed based on linear model and shifting from this theory make changes in radiation protection principles. These biological paradigms at low doses make estimation of low dose ionizing radiation risk estimation more difficult than ever.