COMMENTS ON gLOW-DOSE CANCER RISKh Japan Health Physics Society (JHPS) Working Group on International Issues* Our comments are provided below based on the consensus in the Working Group. We hope Committee 1 will take our comments into account for a better foundation document. 1. Source of Epidemiological Data (in Chapter 2) As the final goal of radiation biology in relation to radiological protection is to understand the effects of low level radiation on human beings, it is reasonable to have epidemiology at the beginning of the report. Chapter 2 summarizes the epidemiological data among cohorts having received medical exposure and exposure under industrial situation as well as A-bomb survivors. Without doubt each of them is very informative; however, we have another set of data which should be taken into consideration. Those are data from research works on health effects of those living in high natural background radiation area. The strength of these data are as follows; (1) they cover both males and females, (2) they cover all ages, (3) the exposure is protracted one at low dose rate, (4) the exposure was under non-stressful situation compared to medical exposures and A-bomb survivors. These data have accumulated and many qualified papers have been published to demonstrate that there was not any increase in cancer mortality in high background areas compared to control areas. 2. Mammary Tumor Induced by Fluoroscopy (in Chapter 2) The Committee concluded that there was epidemiological evidence, of linking increased cancer risk to exposures at doses on the order of 10 mGy. However, most of these cases are exposed to multiple exposures and the total dose was much higher; for example, in the case of mammary tumor among women given multiple fluoroscopy examination, the total dose reached a few Gy or more iRadiat. Res. 145: 694-707, 1996j. It should not be reasonable, therefore, to refer these cases as an example for the increase in cancer by exposure at the order of 10 mGy. 3. Origin of Intra-/Inter-Cellular Signals (in Chapter 3) DSB of DNA is the most important cause of biological effects as described in Chapter 3. DSBs are also significant origin of intra-/inter-cellular signals; however, recently we have a lot of evidences that cellular membrane is also the origin of signals affecting cellular radiosensitivity (Cell Mol Biol 47, 473-84, 2001). Cellular Membrane should be also considered as important origin of signals which affect responses of a cell or cell population to ionizing radiation. 4. Small Amount of Remaining Damage after Low Level Exposure (in Chapter 3) As is discussed in Chapter 3, it was reported that DSB was not repaired when its amount was small. This is mentioned as an example that the DSB rejoining was not perfect; however, this phenomenon should be a part of the mechanism to remove those cells containing potentially carcinogenic damage as described the original paper (Proc. Natl. Acad. Sci. USA.100, 5057-5062, 2003). 5. Linearity of Dose Responses for Carcinogenesis (in Chapter 3) As discussed in Chapter 3, LNT hypothesis is based on the facts (1) even a single track of radiation would induce clustered damage and (2) the repair cannot be error-free. These discussions are reasonable at cellular level. In the process of tumorigenesis there are certain defense mechanisms of higher level, including immune system. Again, those mechanisms are not error free; however the efficiency of the protective functions would be higher for lower doses and dose rates. Inclusion of further explanation of higher level defense mechanisms might be useful although the importance of cellular interaction was described in Chapter 4. U. Bystander Effects and Genomic Instability: Implication for Risk Assessment (in Chapter 4) The bystander effects and genomic instability have generally been tended to be discussed in the context that they would increase the risk from low dose radiation. In the Report (Chapter 4), however, important points are made: (1) both responses are dependent of the genetic background and they cannot be a general rule. (2) Investigation should be continued on the mechanisms underlying these phenomena and their relevance in radiological protection should be discussed based on scientific data. V. Uncertainty (in Chapter 6) The importance of uncertainty in risk assessment is emphasized in Chapter 6. Those factors described in this chapter as sources of uncertainty include both intrinsically uncertain ones, such as that associated with dose estimation, and those uncertainties due to our limited knowledge. Among the uncertainty sources of the latter category, the difference between males and females, difference between populations should be taken into consideration in the radiological protection. Similarly, the age dependency and the difference among individuals should be reflected in radiation regulation. W. Gradualism (in Chapter 6) The concept of gradualism is very reasonable from the view of radiation biology. As discussed in Chapter 6 lots of data suggest that the biological effect tend to be attenuated when dose and/or dose rate decrease. In other words, DDREF should be larger for lower dose and/or dose rate. Therefore, DDREF should be defined as a function of both dose and dose rate. Although currently DDREF is 2; the value of DDREF should be much larger toward zero dose in the ggradualism functionh. Considering the importance of the concept of gradualism, it is disappointing that it is not fully taken into consideration in the report. Committee 1 should emphasize the importance of this concept and suggest a more reasonable basis for radiological protection based on the concept of gradualism. XDAppropriateness of LNT Hypothesis One of the most important conclusion of the present Report is that due to the uncertainty involved in the estimation of risks from low level radiation, we cannot conclude that there is a threshold or not. This is a scientific conclusion and it proposes further investigation of radiation biology at low dose and dose rate. 10. Conclusion The report is, as a whole, very informative review of current knowledge in radiation biology in relation to radiological protection. Especially the concept of the uncertainty and the gradualism should influence on the framework of radiological protection. These concepts should be taken into consideration for more reasonable system for radiological protection. The Working Group on International Issues in Japan Health Physics Society* Chair: K. Fujimoto, National Institute of Radiological Sciences T. Iimoto, The University of Tokyo N. Ishigure, National Institute of Radiological Sciences T. Kikuchi, Jichi Medical School Radioisotope Center S. Miyazaki, The Kansai Electric Power Co., INC. K. Oda, Kobe University K. Sakai, Central Research Institute of Electric Power Industry K. Saito, Japan Atomic Energy Research Institute K. Shinohara, Japan Nuclear Cycle Development Institute I. Urabe, Fukuyama University K. Yamaguchi, Osaka University Hospital