THE MEANING OF LINEAR DOSE-RESPONSE RELATIONS, MADE EVIDENT BY USE OFABSORBED DOSE TO THE CELL

Experimental evidence shows that if the probability of biological resp onse is plotted against the absorbed dose from ionizing radiation, and if both dose and response are determined at the same level of biologi cal organization (e.g., cell or organ-organism) the result appears as a sigmoid, medical-toxicological type of ''dose-response'' function wh en plotted using linear coordinates. However, if the biological respon se expressed at the cellular level is similarly plotted against the av erage absorbed dose expressed at the organ-organism level, a linearly proportional, ''non-threshold'' function is obtained. To explain this marked difference in curve shape, the absorbed dose at the organ level in terms of its meaning at the cellular level was examined, and both dose and response were put on the latter level. The result is consiste nt with the conclusion that absorbed dose at the organ-organism level can be treated, at the cellular level, as the product of two quantitie s: 1) the mean energy concentration or dose in a cell from a depositio n event, i.e.,''hit size'' (the frequency-averaged specific energy in a reference cell target), and 2) the number of deposition events, or ' 'hits,'' on the exposed cells. When the mean hit size for a given radi ation remains constant, and the number of hits is increased, the total number of responses follows a linearly proportional ''hit number resp onse function.'' However, if the hit number is held constant or normal ized to a given value, and the hit size is varied, the resulting proba bility of cell response again plots as the apparently sigmoid curve me ntioned above, which has been termed the ''hit size effectiveness func tion.'' With decreasing hit size, the probability of a cellular respon se appears to decrease asymptotically, and become indistinguishable fr om zero before zero dose is reached. It follows from this inherent rel ationship between the two kinds of functions that a sufficiently exten sive set of data on a population of cells permits either type of funct ion to be produced at will. These findings bear on the interpretation of the ''linear, non threshold'' hypothesis.