Bush__The_Essential_Physics_for_Medical_Imaging - Biomedical ...

anaphasic separation. The extent of the total genetic damage transmitted with chromosomalaberrations depends on a variety of factors, such as the cell type, the numberand kind of genes deleted, and whether the lesion occurred in a somatic or in agametic cell.Chromosomal aberrations are known to occur spontaneously. The scoring ofchromosomal aberrations in human lymphocytes can be used as a biologic dosimeterto estimate the dose of radiation received after an accidental exposure. T lymphocytesare cultured from a sample of the patient's blood and then stimulated todivide, allowing a karyotype to be performed. The cells are arrested at metaphase,and the frequency of rings and dicentrics is scored. Total body doses in excess of0.25 Gy (25 rad) can be detected in this way. Although these chromosomal aberrationsare gradually lost from circulation, they do persist for a considerable periodafter the exposure and can still be detected in the survivors of the atomic bombs inHiroshima and Nagasaki, more than 50 years later.Cellular RadiosensitivityAlthough a host of biologic effects are induced by radiation exposure, the study ofradiation-induced cell death (often defined as the loss of reproductive integrity) isparticularly useful in assessing the relative biologic impact of various types of radiationand exposure conditions. The use of reproductive integrity as a biologic effectsmarker is somewhat limited, however, in that it is applicable only to proliferatingcell systems (e.g., stem cells). For differentiated cells that no longer have the capacityfor cell division (e.g., muscle and nerve cells), cell death is often defined as lossof specific metabolic functions.Cells grown in tissue culture that are lethally irradiated may fail to show evidenceof morphologic changes for long periods; however, reproductive failure eventuallyoccurs. The most direct method of evaluating the ability of a single cell to proliferateis to wait until enough cell divisions have occurred to form a visible colony.Counting the number of colonies that arise from a known number of individual cellsirradiated in vitro and cultured provides a way to determine easily the relativeradiosensitivity of particular cell lines, the effectiveness of different types of radiation,or the effect of various environmental conditions. The loss of the ability toform colonies as a function of radiation exposure can be described by cell survivalcurves.Survival curves are usually presented with the radiation dose plotted on a linearscale on the x-axis and the surviving fraction of cells plotted on a logarithmicscale on the y-axis. The response to radiation is defined by three parameters: theextrapolation number (n), the quasithreshold dose (D q ), and the Do dose (Fig. 25-5). The extrapolation number is found by extrapolating the linear portion of thecurve back to its intersection with the y-axis. This number is thought to representeither the number of targets (i.e., critical molecular sites) in a cell that must be "hit"once by a radiation event to inactivate the cell or the number of "hits" required ona single critical target to inactivate the cell. The extrapolation number for mammaliancells ranges between 2 and 10. The Do describes the radiosensitivity of thecell populationunder study. The Do dose is the reciprocal of the slope of the linear