Microdosimetric Approach to the Analysis of Cell Responses at Low Dose and Low Dose Rate

An approach to the problem of radiation response is proposed and described by which effects produced at low doses and dose rates can be understood as the consequences of radiation absorption events in the nucleus of a single relevant cell and in its DNA. Radiation quality appears as the consequence of two related probabilities, that of energy deposition in the cell nucleus and that of energy deposition in DNA. The starting point is a "gross sensitive volume", GSV, identified with an average mammalian cell nucleus and composed of smaller sensitive volumes, identified with some critical parts of the DNA genome. The GSV leads to the definitions of an "elemental dose", the "integral probability of responses of the GSV population", and the smaller volumes lead to a "relative local efficiency". This approach is applied to various biological endpoints illustrating its merits. The level of dose below which the fraction of hit cells depends linearly on absorbed dose and is independent of dose rate, is delineated. Finally, guide lines for designing low dose and low dose rate experiments are proposed.