Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure

The Therapeutic use of Radon: A Biomedical Treatment in Europe; An “Alternative” Remedy in the United States

There is a growing recognition in the United States and Europe that health care is driven to a significant extent by an emphasis on consumer choice and demand. As consumers, people regularly choose their own solutions for health promotion and maintenance, solutions which may or may not be sanctioned by mainstream medicine. Radioactive radon therapy exemplifies a non-sanctioned treatment eagerly sought by certain patients, but scorned or dismissed by many physicians. This is certainly the case in the United States, where well-publicized Environmental Protection Agency (EPA) warnings portray radon as a potential carcinogen. Between 1997 and 2001, I worked with a population of arthritis sufferers who expose themselves to radon gas in Montana radon health mines in order to alleviate their symptoms. In this paper I discuss the decision-making process involved in using radon, and compare the Montana radon health mine facilities with selected radon mines and spas in Europe

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

A multistage cancer model that describes the putative rate-limiting steps in carcinogenesis is developed and used to investigate the potential impact on cumulative lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In the model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired or unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model explicitly accounts for cell birth and death processes, the clonal expansion of initiated cells, malignant conversion, and a lag period for tumor formation. Radioprotective mechanisms are incorporated into the model by postulating dose and dose-rate-dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. As currently formulated, the model is most applicable to low-linear-energy-transfer (LET) radiation delivered at low dose rates. Sensitivity studies are conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose-rate-dependent cellular defense mechanisms are incorporated into a multistage cancer model. For lung cancer, both linear no-threshold (LNT-), and non-LNT-shaped responses can be obtained. If experiments demonstrate that the effects of DNA damage repair and radical scavenging are enhanced at least three-fold under low-dose conditions, our studies would support the existence of U-shaped responses. The overall fidelity of the DNA damage repair process may have a large impact on the cumulative incidence of lung cancer. The reported studies also highlight the need to know whether or not (or to what extent) multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years) for low-LET radiation