The influence of concentration of DNA on the radiosensitivity of mammalian cells

Purpose: To develop relations that explicitly show the dependence of the linear-quadratic survival parameters alpha and beta on the nuclear volume, average DNA concentration, and degree to which the chromatin is condensed in zones of the nucleus. Methods and Materials: The microdosimetric-kinetic model of mammalian cell killing is used. Results: The relations indicate an increased tendency for lethal lesions to form by pairwise combination of potentially lethal lesions in regions of relatively greater local DNA concentration. In particular, the value of beta is proportional to the average nuclear concentration of DNA and to a parameter that reflects the condensation of DNA into a relatively concentrated phase, such as occurs in mitotic chromosomes and heterochromatin. These relations indicate local DNA concentration in the nucleus is a significant determinant of three magnitude of beta. Because alpha is composed of a term that is proportional to beta it is also affected by DNA concentration, generally to equal or less degree. Conclusion: It may be possible to establish a correlation between nuclear size and morphology, as determined from microscope slides prepared from biopsy specimens, with radiation sensitivity and the alpha/beta ratio that could be useful in radiation treatment planning. (c) 2005 Elsevier Inc.