tJ "ad iological Indicators Bond only early acute 0 radiation expo- \ ! 2 go 3 2 0.01 0.0014 ; poor 0,000 isual curve (Fig. louse, the fraction - (dying), is plot- » obtain the usual e first derivative 7 7 7 7 7 r inimals [1]. It is il 30 day mortal- cell survival, obtained by using the 7Ti// and McCullough spleen colony assay. The curve represents composite data obtained over the course of years by the hematology group in the Medical Department at Brookhaven. Of the ting from deple- ion in the bone ithreference to ‘system ofinter- many such curves that have been obtained with ich are the stem Fig. 1). 084 % o4- E 0.34 A 024 ° + The first constituent function of the doseresponse curve in Figure 2 is shown in Figure 3. This is simply a “dose-effect” curve. for stem ype distribution, e distribution of photons, most appear to have no “shoulder.” However. occasionally a small shoulder may appearto be present. The function is dotted from In Figure 4, and with reference first to the left ordinate only. one sees (“cell survival” curve) the same function plotted in Figure 3, but now on arithmetic rather than semi-logarithmic coordinates. However, also shownis the inverse ofthis curve, representing the severity of effect on the , . + 8 1 2 3 4 5 Dose (Gy) é = 8 8 . r 30 $f : 4 =5 P40 3 e; ec oe F 60 q 20 , ? bh 8 9 0 permits one to obtain a quantitative measure of the severity of effect on the parent organ system. Theresults of thus using severity of effect as the independent variable is shown in Figure 5. Note that the scale for severity of effect is simplythe fraction (or percentage) of stem cells killed, which mustof course saturate at 1.0 (100% ). The resulting curve is extraordinarily steep: however, this is merely a matter of scaling. If one expands the scale (Fig. 6). the S-shaped curveis regained. It is then also obvious that the severity of effect can be used as the independent variable, in terms of which the mortality rate of the ani' mals maybe described and thus predicted. It becomesclearthat. if one does have a quantitative wo 9080-1 % Mouse Mortality e : NL 2 - $0 Mouse Mortality —= Call Survival 70 Fig. 4. Plot showing the relationships among the curves for stem cell survival. severity of organ effect and mouse mortalityrate. all as a function of dose. about 6 Gy on becauseof technical difficulties associated with having to inject large numbers of bone marrowcells in order to detect the few remaining viable stem cells. Ss : t j8 Fig. 3. A conventional plot for the log of the fraction of surviving colony-forming units-spleen (CFU-S)(hematopoietic stem cells) as a function of dose. The fitted function intersects the ordinate ata value somewhatabove unity indicating that the curve mayhave a small shoulder. oroken downinto + 80 .:: 06-4 ony ale of severity of dicine, it is first dose mortality ammarays deliv- 100 i - i of Organ Effect ~ Severity 07-4 2 a 7 Q G 084 ° * Stern Cell Survival (CFU-S) mortality in the ‘ators must be and | a high degree of arly cancer where roblematical. will i of 094 70-7 relevant organ, the bone marrow. When thefrac- tion of the remaining stem cells becomes quite low, on the order of less than !% (meaning that the effect on the relevant organ. the bone marrow, Is severe indeed), the more sensitive animals begin to die, forming the initial part of the mortality response curve indicated on the right ordinate. It is then obvious that the mortality rate erence ? a 9 ” response funciber of animals ‘the dose of the i¥S}. These data amongthe cellular elements of the organ system can be used as a “biological indicator,” which -@ (BNL) strain. aU | OG £3x a f {, 4 i i 0 O11 OF O3 O48 OS O8 OF O8 O08 ! Severity of Effect Fig. 5. The second constituent curve. for mouse mortality as a function ofthe severity of effect on the bone marrow. Note that the line is indistinguishable from linear. but does deviate slightly trom the vertical. ay e—“(tisSOsOSCSCsCsC‘(‘(aESCUO;O(éit,Gg