This hypothesis that all radiation is harmful in linear proportion to the dose, is the principle used for collective dose calculations of the number of deaths produced by any radiation, natural of generated, no matter how small. The National Council of Radiation Protection and Measurements Report 121, "Principles and Application of Collective Dose in Radiation Protection," summarizes the basis for adherence to linearity of radiation health effects.3
"Taken as a whole, the body of evidence from both laboratory animals and human studies allows a presumption of a linear no threshold response at low doses and low dose-rates, for both mutations and carcinogenesis. Therefore, from the point of view of the scientific bases of collective doses for radiation protection purposes, it is prudent to assume the effect per unit dose in the low-dose region following single acute exposures or low-dose fractions in a linear response. There are exceptions to this general rule of no threshold, including the induction of bone tumors in both laboratory animals and in some human studies due to incorporated radionuclides, where there is clearly evidence for an apparent threshold.NCRP Report 121 summarizes that while some studies "provide quantitative data that, with statistical significance, contradict the concept of collective dose," "ultimately, confidence in the linear no threshold dose-response relationship at low doses [LNT hypothesis] is based on our understanding of the basic mechanisms involved." Current understanding of the basic biologic mechanisms involved and recent data that contradict the LNT hypothesis. The biologic data also contradict "the presumption, based on biophysical concepts, which provides a basis for the use of collective dose in radiation protection activities."However, few experimental studies, and essentially no human data, can be said to prove or even to provide direct support for the concept of collective dose with its implicit uncertainties of nonthreshold linearity and dose-rate independence with respect to risk. The best that can be said is that most [sic] studies do not provide quantitative data that, with statistical significance, contradict the concept of collective dose.
Ultimately, confidence in the linear no threshold dose-response relationship at low doses is based on our understanding of the basic mechanisms involved. Genetic effects may result from a gene mutation, or a chromosome aberration. The activation of a dominant acting oncogene is frequently associated with leukemias and lymphomas, while the loss of suppressor genes appears to be more frequently associated with solid tumors. It is conceptually possible, but with a vanishing small probability, that any of these effects could result from the passage of a single charged particle, causing damage to DNA that could be expressed as a mutation or small deletion. It is a result of this type of reasoning that a linear nonthreshold dose-response relationship cannot be excluded. It is this presumption [sic], based on biophysical concepts, which provides a basis for the use of collective dose in radiation protection activities."
Dr. Zbigniew Jaworowski, past chairman of UNSCEAR, in his current review of hormesis cites recent data showing hormetic effects in humans from the former Soviet Union.5 After radiation exposure from a thermal explosion in 1957, 7852 persons living in 22 villages in the Eastern Urals were divided into three exposure groups averaging 49.6 cGy, 12.0 cGy, and 4.0 cGy and followed for 30 years. Tumor related mortality was 28%, 39% abd 27% lower in the 49.6 cGy, 12.0 cGy and 4.0 cGy groups, respectively, than in the nonirradiated control population in the same region. In the 49.6 cGy and 12.0 cGy groups the difference from the controls was statistically significant. (Figure 1) Epidemiologic studies showing beneficial effects of low doses of radiation in atomic bomb survivors (Figure 2) and other populations were reviewed by Sohei Kondo, Professor of Radiation Biology, Atomic Energy Research Institute, Kinki University, Osaka, Japan.6 Included are the apparently beneficial effects of low doses of external gamma rays on the life span of radium-dial painters and the significantly lower mortality from cancers at all sites of residents of Misasa, an urban area with radon spas, than residents of the suburbs of Misasa (Figure 3).
These beneficial effects are consistent with the findings of B.L. Cohen, Professor of Physics, University of Pittsburgh, that relate the incidence of lung cancer to radon exposure in nearly 90% of the population of the United States.7 The 1601 counties selected for adequate permanence of residence provide extremely high-power stastical analysis. After applying the BEIR IV8 correction for variations in smoking frequency, the study shows a very strong tendency for lung cancer mortality to decrease with increasing mean radon level in homes, in sharp contrast to the BEIR IV theoretical increased mortality derived by linear no threshold extrapolation of effects in uranium miners exposed to very high radon concentrations. The discrepancy between theoretical and measured slopes is 20 standard deviations (Figure 4). Rigorous statistical analysis of 54 socioeconomic, seven physical, and multiple geographic variables as possilbe confounding factors, both single and in combination, demonstrates no significant decrease in the discrepancy. The multiple independent requirements that a possilbe unknown confounding factor mus meet, make its existence highly improbable. A resonable explanantion is that stimulated biological mechanisms more than compensate for the radiation "insult" and are protective against cancer in a low-dose, low-dose-rate range.
The thirteen-year U.S. Nuclear Shipyard Workers study of the health effects of low-dose radiation was performed by the Johns Hopkins Department of Epidemiology, School of Public Health and Hygiene, reported to the Department of Energy in 19919 and reported in UNSCEAR 1994.4 Professor Arthur C. Upton, who concurrently chaired the NAS BEIR V Committee on "Health Effects of Exposure to Low Levels of Ionizing Radiation,"10 chaired the Technical Advisory Panel that advised on the research and reviewed the results.
The results of this study contradict the conclusions of the BEIR V report10 that small amounts of radiation have risk - the LNT hypothesis. From the database of almost 700,000 shipyard workers, including about 108,000 nuclear workers, three closely matched study groups were selected, consisting of 28,542 nuclear workers with working lifetime doses ³ 5 mSv (many received doses well in excess of 50 mSv), 10,462 nuclear workers with doses < 5 mSv and 33,352 non-nuclear workers. Deaths in each of the groups were classified as due to: all causes, leukemia, lymphatic and hematopoietic cancers, mesothelioma, and lung cancer. The results demonstrated a statistically significant decrease in the standardized mortality ratio for the two groups of nuclear workers for "death from all causes" compared with the non-nuclear workers. For the ³ 5 mSv group of nuclear workers, the highly significant risk decrement to 0.76, 16 standard deviations below 1.00, of the standard mortality ratio for death from all causes is inconsistent with the LNT hypothesis and dose not appear to be explainable by the healthy worker effect (Figure 5).4 The non-nuclear workers and the nuclear workers were similarly selected for employment, were afforded the same health care thereafter, and performed the identical type of work, except for exposure to 60Co gamma radiation, with a similar medial age of entry into employment of about 34 years. This provides evidence with extremely high statistical power that low levels of ionizing radiation are associated with risk decrements.
Nevertheless, Professor Arthur C. Upton and others consider the three-country low-dose radiation and cancer study of Cardis, et al.11, 12, to be the best occupational study of nuclear workers (Figure 6). This study concluded, " There was no evidence of an association between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic, lymphocytic leukemia (CLL) ...was significantly associated with cumulative external radiation dose (one-sided P value = 0.046: 119 deaths)." The statistical methods used state: "As there was no reason to suspect that exposure to radiation would be associated with a decrease in risk of any specific type of cancer, one-sided tests are presented throughout." The author's analysis of the 119 deaths from all leukemias except CLL excluded 86 deaths in dose categories 1.3.4, and 6 in which there were fewer deaths than expected. Trend analysis of the remaining 33 deaths in dose categories 2,5 and 7 for estimated P=0.046 was obtained "using computer simulations based on 5000 samples, rather than the normal approximation."11
The Canadian Breast Cancer Fluoroscopy Study13 reports the observations of the mortality from breast cancer in a cohort of 31,710 woman who had been examined by multiple fluoroscopy between 1930 and 1952. The observed rates of mortality are related to breast radiation doses and presented only in tabular form. The authors compare linear and linear-quadratic dose-response models fit to the data and conclude, "that the most appropriate form of dose-response relations is a simple linear one, with different slopes for Nova Scotia and the other provinces." On the basis of this linear model that includes only non-significant data and excludes the data with the highest confidence limits (Figure 7), the authors predict the lifetime excess risk of death from breast cancer after a single exposure at age 30 to 1 cGy(1r) to be approximately 60 per million women or 900 per million women exposed to 15 cGy. The observed data, however, demonstrate with high statistical confidence, a reduction of the relative risk of breast cancer to 0.66 (P=0.05) at 15 cGy and 0.85 (P=0.32) at 25 cGy. The second author, in his 1996 revision of this study, removed this highly significant contradiction of the LNT hypothesis by lumping all low-dose data into a single 1-49 cGy category.14 The study actually predicts that a dose of 15 cGy would be associated with 7,000 fewer deaths in these million women. Lauriston S. Taylor, past president of the NCRP, consider application of LNT theory for calculations of collective dose as, "deeply immoral uses of our scientific heritage"15.
Metabolic and Radiation DNA Damage ControlDuring the past decade rapid advances in our knowledge of molecular biology and cell function enable us to understand why low-dose radiation is associated with positive health effects in contrast to the carcinogenic effect of high-dose radiation. Our understanding is based upon current, cellular molecular biology observations. Estimates are based on published data and recent personal communications:
The efficiency of this biosystem is increased by the adaptive responses to low-dose ionizing radiation (Figures 9, 10). This is well documented in UNSCEAR 1994.4
"There is substantial evidence that the number of radiation-induced chromosomal aberrations and mutations can be reduced by a small prior conditioning dose in proliferating mammalian cells in vitro and in vivo.This statement applies not only to the mutations produced by radiation and other toxic agents, but also to the unmentioned enormous number of daily metabolic mutations. The operative effect of reducing metabolic mutations by the adaptive response of the damage-control biosystem to low-dose radiation is the critical factor, not reduction of the relatively negligible number of mutations produced by low-dose radiation. This critical factor must be considered, "to judge the balance between stimulated cellular repair and residual damage."There is increasing evidence that cellular repair mechanisms are stimulated after radiation-induced damage... Whatever the mechanisms, they seem able to act not only on the lesions induced by ionizing radiation but also on at least a portion of the lesions induced by some other toxic agents.
As to the biological plausibility of a radiation-induced adaptive response, it is recognized that the effectiveness of DNA repair in mammalian cells is not absolute... An important question, therefore, is to judge the balance between stimulated cellular repair and residual damage."
Assuming a 20% increased efficiency of biosystem control in response to a tenfold increase of annual background radiation from 0.1cGy/y to 1cGy/y, radiation mutations would indeed increase from 1x10-7/cell/d to 8x10-7/cell/d but metabolic mutations would decrease from ~1/cell/d to ~0.8/cell/d (Figure 11).17 "The balance between stimulated cellular repair and residual damage" is a decrease of mutations for an average of ~1 mutation/cell/d to ~0.8 mutation/cell/d (Figures 8, 11)17
UNSCEAR did not consider that the increase of radiation mutations is negligible compared to the operative effect of the adaptive response to low-dose radiation upon the high-background of metabolic mutations. The biologic effect of radiation is not determined by the number of DNA mutations it creates, but by its effect on the biosystem that controls the relentless enormous burden of oxidative DNA damage. High-dose radiation impairs this biosystem with consequent significant increase of metabolic mutations and corresponding risk increments. Low-dose radiation stimulates the DNA damage-control biosystem with consequent significant decrease of metabolic mutations and corresponding risk decrements (Figures 8, 9, 10, 11).35
This reduction of gene mutations in response to low-dose radiation provides a biological explanation of the statistically significant observations of mortality and cancer mortality risk decrements, and contradicts the biophysical understanding of the basic mechanisms upon which, ultimately, the NCRP's confidence in the LNT hypothesis is based.
This article represents the views of the author and not necessarliy those of the U.S. Nuclear Regulatory Commission.