Dose-Response: An International Journal
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Welcome to Nonlinearity in Biology, Toxicology and Medicine
Calabrese, Edward J.
Health Effects of High Radon Environments in Central Europe: Another Test for the LNT Hypothesis?
Becker, Klaus
Among the various "natural laboratories" of high natural or technical enhanced natural radiation environments in the world such as Kerala (India), Brazil, Ramsar (Iran), etc., the areas in and around the Central European Ore Mountains(Erzgebirge) in the southern parts of former East Germany, but also including parts of Thuringia, northern Bohemia (now Czech Republic), and northeastern Bavaria, are still relatively little known internationally. Although this area played a central role in the history of radioactivity and radiation effects on humans over centuries, most of the valuable earlier results have not been published in English or quotable according to the current rules in the scientific literature and therefore are not generally known internationally. During the years 1945 to 1989, this area was one of the world's most important uranium mining areas, providing the former Soviet Union with 300,000 tons of uranium for its military programs. Most data related to health effects of radon and other carcinogenic agents on miners and residents became available only during the years after German reunification. Many of the studies are still unpublished, or more or less internal reports. By now, substantial studies have been performed on the previously unavailable data about the miners and the population, providing valuable insights that are, to a large degree, in disagreement with the opinion of various international bodies assuming an increase of lung cancer risk in the order of 10% for each 100 Bq/m3 (or doubling for 1000 Bq/m3), even for small residential radon concentrations. At the same time, other studies focusing on never-smokers show little or no effects of residential radon exposures. Experiments in medical clinics using radon on a large scale as a therapeutic against various rheumatic and arthritic disease demonstrated in randomized double-blind studies the effectiveness of such treatments. The main purpose of this review is to critically examine, including some historical references, recent results primarily in three areas, namely the possible effects of the inhalation of very high radon concentrations on miners; the effect of increased residential radon concentrations on the population; and the therapeutic use of radon. With many of the results still evolving and/or under intense discussion among the experts, more evidence is emerging that radon, which has been inhaled at extremely high concentrations in the multimillion Bq/m3 range by many of older miners (however, with substantial confounders, and large uncertainties in retrospective dosimetry), was perhaps an important but not the dominating factor for an increase in lung cancer rates. Other factors such as smoking, inhalation of quartz and mineral dust, arsenic, nitrous gases, etc. are likely to be more serious contributors to increased miner lung cancer rates. An extrapolation of miner data to indoor radon situations is not feasible. Concerning indoor radon studies, the by far dominating effect of smolung on the lung cancer incidence makes the results of some studies, apparently showing a positive dose-response relationship, questionable. According to recent studies in several countries, there are no, or beneficial, residential radon effects below about 600 to 1000 Bq/m3 (the extensive studies in the U.S., in particular by B. Cohen, and the discussions about these data, will not be part of this review, because they have already been discussed in detail in the U.S. literature). As a cause of lung cancer, radon seems to rank - behind active and passive smoking, and probably also air pollution in densely populated and/or industrial areas (diesel exhaust soot, etc.) - as a minor contributor in cases of extremely high residential radon levels, combined with heavy smoking of the residents. As demonstrated in an increasing number of randomized double-blind clinical studies for various painful inflammatory joint diseases such as rheumatism, arthritic problems, and Morbus Bechterew, radon treatments are beneficial, with the positive effect lasting until at least 6 months after the normally 3-week treatment by inhalation or bathes. Studies on the mechanism of these effects are progressing. In other cases of extensive use of radon treatment for a wide spectrum of various diseases, for example, in the former Soviet Union, the positive results are not so well established. However, according to a century of radon treatment experience (after millenniums of unknown radon therapy), in particular in Germany and Austria, the positive medical effects for some diseases far exceed any potential detrimental health effects. The total amount of available data in this field is too large to be covered in a brief review. Therefore, less known - in particular recent - work from Central Europe has been analyzed in an attempt to summarize new developments and trends. This includes cost/benefit aspects of radon reduction programs. As a test case for the LNT (linear non-threshold) hypothesis and possible biopositive effects of low radiation exposures, the data support a nonlinear human response to low and medium-level radon exposures.
Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses
Liu, De Li; An, Min; Johnson, Ian R.; Lovett, John V.
Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the allelochemical effects. The model is compared with experimental data for the response of lettuce seedling growth to Centaurepensin, the olfactory response of weevil larvae to α-terpineol, and the responses of annual ryegrass (Lolium multiflorum Lam.), creeping red fescue (Festuca rubra L., cv. Ensylva), Kentucky bluegrass (Poa pratensis L., cv. Kenblue), perennial ryegrass (L. perenne L., cv. Manhattan), and Rebel tall fescue (F. arundinacea Schreb) seedling growth to leachates of Rebel and Kentucky 31 tall fescue. The results show that the model gives a good description to observations and can be used to fit a wide range of dose responses. Assessments of the effects of leachates of Rebel and Kentucky 31 tall fescue clearly differentiate the properties of the allelopathic sources and the relative sensitivities of indicators such as the length of root and leaf. allelopathyallelochemicalsmathematical modellingstimulationdose-response relationshipinverted U-shape response.
Decomposition Analyses Applied to a Complex Ultradian Biorhythm: The Oscillating NADH Oxidase Activity of Plasma Membranes Having a Potential Time-Keeping (Clock) Function
Foster, Ken; Anwar, Nasim; Pogue, Rhea; MorrE, Dorothy M.; Keenan, T. W.; Morr', D. James
Seasonal decomposition analyses were applied to the statistical evaluation of an oscillating activity for a plasma membrane NADH oxidase activity with a temperature compensated period of 24 min. The decomposition fits were used to validate the cyclic oscillatory pattern. Three measured values, average percentage error (MAPE), a measure of the periodic oscillation, mean average deviation (MAD), a measure of the absolute average deviations from the fitted values, and mean standard deviation (MSD), the measure of standard deviation from the fitted values plus R-squared and the Henriksson-Merton p value were used to evaluate accuracy. Decomposition was carried out by fitting a trend line to the data, then detrending the data if necessary, by subtracting the trend component. The data, with or without detrending, were then smoothed by subtracting a centered moving average of length equal to the period length determined by Fourier analysis. Finally, the time series were decomposed into cyclic and error components. The findings not only validate the periodic nature of the major oscillations but suggest, as well, that the minor intervening fluctuations also recur within each period with a reproducible pattern of recurrence. biological clockdecomposition analysesultradian rhythmtemperature compensationcircadian rhythmcultured cells.
Nonlinear Dose-Response Relationship in the Immune System Following Exposure to Ionizing Radiation: Mechanisms and Implications
Lui, Shu-Zheng
The health effects of low-dose radiation (LDR) have been the concern of the academic spheres, regulatory bodies, governments, and the public. Among these effects, the most important is carcinogenesis. In view of the importance of immune surveillance in cancer control, the dose-response relationship of the changes in different cell types of the immune system after whole-body irradiation is analyzed on the basis of systemic data from the author's laboratory in combination with recent reports in the literature. For T lymphocytes J- or inverted J-shaped curves are usually demonstrated after irradiation, while for macrophages dose-response curves of chiefly stimulation with irregular patterns are often observed. The intercellular reactions between the antigen presenting cell (APC) and T lymphocyte (TLC) in the immunologic synapse via expression of surface molecules and secretion of cytokines by the two cell types after different doses of radiation are illustrated. The different pathways of signal transduction thus facilitated in the T lymphocyte by different doses of radiation are analyzed to explain the mechanism of the phenomenon of low-dose stimulation and high-dose suppression of immunity. Experimental and clinical data are cited to show that LDR retards tumor growth, reduces metastasis, increases the efficacy of conventional radiotherapy and chemotherapy as well as alleviates the suppression of immunity due to tumor burden. The incidence of thymic lymphoma after high-dose radiation is lowered by preexposure to low-dose radiation, and its mechanism is supposed to be related to the stimulation of anticancer immunity induced by low-dose radiation. Recent reports on lowering of standardized cancer mortality rate and all cause death rate of cohorts occupationally exposed to low-dose radiation from the US, UK, and Canada are cited. dose-response curvesimmune surveillancemolecular and cellular mechanismscancer risk.