Fa Ser eG repository BOX Ne. -DICAL TRANSMISSION SCANNIAR FOLDER t243¢% is. Wiley-Liss, Inc. Brookhaven National Labora .o: SSI in Upton, L, L, New York #92. "C. Meissner A. 10N On tumor inci; for radiation ther3-436, Dose, Effect Severity, and Imparted Energy in Assessing Biological Effects ) threshold theory of ihaled radon energy 995-68 :157-174. Brookhaven National Laboratory, Medical Department, Upton, New York. USA 4016840 V. P. Bond Key Words. Cancer ¢ Absorbed dose * Imparted energy ¢ Severity of effect « Quantal biological response * Medicine versus public health Abstract. Because of the widespread efforts in cancer radioepidemiological studies to attach a value of absorbed dose to each exposed individual, the notion seems to have become prevalent that dose plays an essential role in the medical determination of the diagnosis and prognosis of the individual. This view is enhanced by the fact that, while the present quantities and units for radiological physics were developed in the contextof the acute effects of large exposures to radiation, e.g., in radiotherapy wherethey still apply well, these same quantities and units have been used, without modification, to apply to cancer radivepidemiology in the context of low level irradiation. A principle purpose of the present communication is to show that, in medicine, dose plays a limited role even in the deterministic application of therapeutic agents, and that diagnosis and estimates of prognosis in medicine are based, not on dose, but on the severity of effect on, or dam- age to the organ or organs involved in a particular medical condition. Thusit is “going backward”to view estimates of the severity of effect, e.g., the fraction of cells with abnormalities, or killed, as a “bio- logical dosimeter,” rather than as a quantitative estimate of the severity ofeffect. The use of biological indicators is of maximum value in noncancerousdisease or injury in which the severity of an effect causative for organ failure and a consequent quantal, e.g., a lethal responsein the individual, can be measured with increasing accuracy by modern medical techniques. A commonscale for the measurementof almost any typeof effect on any organis 0.0 to 1.0 (0.0 to 100%), with 100% meaning complete functional failure and certain death if the organ is vital. The opposite extreme is cancer, in which, particularly Correspondence: Dr. Victor P. Bond. Medical Department. Brookhaven National Laboratory, P.O. Box 5000, Upton, NY 11973-5000, USA. Received November 21, 1994; accepted for publication November 21, 1994. ©AlphaMedPress 10665099/95/35 .00/0 3 : em oud LZ ‘| GO STEM CELLS 1995313(suppl1):21-29 a . RETO The Medica] Research Cen ter EPT PVBLICATIONS cevTINUaS, X-RAY sovReg eat bred- GIA a5 PEC rOYT OVS RECORDS conection VARSHALL ISLANDS | otection and Repair t with low level irradiation, there is no detectable effect directly relevant to cancer causation. the severity of which will provide an individualized, medical-type diagnosis or prognosis. However, this ~ situation is beginning to change with the rapid development of molecular biology and genic change profiles that may make individualized prognostic estimates possible. However, because neither radiation nor other carcinogens leave “markers,’”’ the impact of these changes with respect to lowlevel irradiation must be left open. introduction Before biological effects and responses of any kind can be assessed objectively, it 1s necessary to review and discuss the various levels of biological organization at which these can occur. In Figure 1 is shown a numberof levels, most of which are both interlocking and recursive. This means that most of the levels can be regarded as a potentially responding system, composed of potentially damaged elements located one or more levels lower on the scale. However, it also means that the identical level can be regarded as a population of elements, severe damage to which may cause a quantal response in their parent system located one or more levels higher up onthescale. In the past, when the dose to a system has been unknownor only poorly known, an observable biological endpoint such as chromosome aberrations in cells, has been used frequently as a “biological dosimeter.” In other words, because the numberof cells with a given aberration determined in an individual is a function of dose, a given level of response can be used to obtain an estimate of the dose received. The implication is thatit is the dose to the individual