A microdosimetric-kinetic theory of the dependence of the RBE for cell death on LET.
Experiments with cultured mammalian cells exposed to ionizing radiation of varying LET are examined in the context of a microdosimetric-kinetic (MK) model of radiation induced mammalian. cell killing similar to the site model of the theory of dual radiation action. The experimentally measured RBE, in the limit of zero dose, increases linearly with LET for LET less than a value that lies in the range of about 40-90 keV per micron. It is shown that the tendency of the RBE to increase linearly with LET can be explained as a result of the random variation of specific energy among microscopic sized domains (sites), into which the nucleus may be partitioned, and the effect of this variation on the formation of lethal lesions by pairwise combination of repairable primary lesions in DNA. the microscopic subunits corresponding to a site have diameter in the range of 0.56-0.75 microns. The linearity of RBE with increasing LET implies that value of the quadratic parameter of the linear-quadratic survival relation (beta) is constant, at least for LET low enough to be in the linear range, and this in turn implies the production of primary DNA lesion, likely double strand breaks, does not increase with LET. the experiments, interpreted with MK model, also imply that the repairability and potential for lethality of the primary DNA lesion does not change with variation of LET within the linear range. The failure of RBE to maintain its linear increase for higher values of LET, and the resulting RBE maximum at about 100 keV per micron, are likely primarily due to the departure of the distribution of lethal lesions among cells from the Poisson distribution. Some implications concerning the use of radiation to treat cancer are noted.
Department of Radiation Oncology, Ochsner Clinic, New Orleans, Louisiana, USA.
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Hawkins
D000818:Animals; D016923:Cell Death / Q000528:radiation effects*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D018499:Linear Energy Transfer / Q000502:physiology* / Q000528:radiation effects*; D008954:Models, Biological; D011874:Radiometry / Q000706:statistics & numerical data; D012062:Relative Biological Effectiveness