Commentary on Inhaled (239)PUO2 in Dogs - A Prophylaxis Against Lung Cancer?
TL;DR: These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.
Abstract: Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.
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TL;DR: This text is a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA.
Abstract: The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.
1,359 citations
TL;DR: A patient with advanced AD in hospice who received 5 computed tomography scans of the brain, about 40 mGy each, over a period of 3 months partially restored cognition, memory, speech, movement, and appetite.
Abstract: Alzheimer disease (AD) primarily affects older adults. This neurodegenerative disorder is the most common cause of dementia and is a leading source of their morbidity and mortality. Patient care costs in the United States are about 200 billion dollars and will more than double by 2040. This case report describes the remarkable improvement in a patient with advanced AD in hospice who received 5 computed tomography scans of the brain, about 40 mGy each, over a period of 3 months. The mechanism appears to be radiation-induced upregulation of the patient's adaptive protection systems against AD, which partially restored cognition, memory, speech, movement, and appetite.
47 citations
TL;DR: The analysed data concerning radon concentrations below ~1000 Bq/m3 (~20 mSv/year of effective dose to the whole body) do not support the thesis that radon may be a cause of any statistically significant increase in lung cancer incidence.
Abstract: A re-analysis has been carried out of thirty-two case-control and two ecological studies concerning the influence of radon, a radioactive gas, on the risk of lung cancer. Three mathematically simplest dose-response relationships (models) were tested: constant (zero health effect), linear, and parabolic (linear-quadratic). Health effect end-points reported in the analysed studies are odds ratios or relative risk ratios, related either to morbidity or mortality. In our preliminary analysis, we show that the results of dose-response fitting are qualitatively (within uncertainties, given as error bars) the same, whichever of these health effect end-points are applied. Therefore, we deemed it reasonable to aggregate all response data into the so-called Relative Health Factor and jointly analysed such mixed data, to obtain better statistical power. In the second part of our analysis, robust Bayesian and classical methods of analysis were applied to this combined dataset. In this part of our analysis, we selected different subranges of radon concentrations. In view of substantial differences between the methodology used by the authors of case-control and ecological studies, the mathematical relationships (models) were applied mainly to the thirty-two case-control studies. The degree to which the two ecological studies, analysed separately, affect the overall results when combined with the thirty-two case-control studies, has also been evaluated. In all, as a result of our meta-analysis of the combined cohort, we conclude that the analysed data concerning radon concentrations below ~1000 Bq/m3 (~20 mSv/year of effective dose to the whole body) do not support the thesis that radon may be a cause of any statistically significant increase in lung cancer incidence.
36 citations
TL;DR: Data show that BPA induced a novel type of podocytopathy characterizes by an impairment of podocyte adhesion, by altering the expression of adhesion and cytoskeleton proteins, which provide a mechanism by which BPA could participate in the pathogenesis and progression of renal diseases.
Abstract: Bisphenol A (BPA), a chemical -xenoestrogen- used in food containers is present in the urine of almost the entire population. Recently, several extensive population studies have proven a significant association between urinary excretion of BPA and albuminuria. The alteration of glomerular podocytes or "podocytopathy" is a common event in chronic albuminuric conditions. Since many podocytes recovered from patients' urine are viable, we hypothesized that BPA could impair podocyte adhesion capabilities. Using an in vitro adhesion assay, we observed that BPA impaired podocyte adhesion, an effect that was abrogated by Tamoxifen (an estrogen receptor blocker). Genomic and proteomic analyses revealed that BPA affected the expression of several podocyte cytoskeleton and adhesion proteins. Western blot and immunocytochemistry confirmed the alteration in the protein expression of tubulin, vimentin, podocin, cofilin-1, vinculin, E-cadherin, nephrin, VCAM-1, tenascin-C, and β-catenin. Moreover, we also found that BPA, while decreased podocyte nitric oxide production, it lead to overproduction of ion superoxide. In conclusion, our data show that BPA induced a novel type of podocytopathy characterizes by an impairment of podocyte adhesion, by altering the expression of adhesion and cytoskeleton proteins. Moreover, BPA diminished production of podocyte nitric oxide and induced the overproduction of oxygen-free metabolites. These data provide a mechanism by which BPA could participate in the pathogenesis and progression of renal diseases.
16 citations
TL;DR: A new treatment system is presented, α-Radiorespiro-Rn, which seems to be extremely effective in treating cancer, and the prospect of using the novel 225Ac-prostate-specific membrane antigen ligand-617 ligand as a therapeutic agent for prostate cancer is discussed.
Abstract: Therapy with α-radiation has issues associated with internal exposure; its clinical use has been avoided. However, phase III clinical tests of the α-emitting nuclide 223Ra on patients with cancer have been conducted, and results were reported in 2011 to 2012. Since then, research has being carried out on targeted internal therapy by introducing α-emitting nuclides directly into the cancers. For many decades, nontargeted radon therapy has been carried out and is controversial because its mechanism of action is stimulation. The low-level radiation sends powerful signals to upregulate many biological protection systems, which protect against the effects of radiogenic and nonradiogenic toxins. These vital systems prevent, repair, and remove DNA and other biomolecular damage being produced endogenously at a very high rate by the very abundant reactive oxygen species associated with aerobic metabolism. Stimulation of protection systems results in beneficial effects, including a lower risk of cancer. This article reports the results of treatments on 4 patients with cancer and reviews the clinical use of α-radiation from 223Ra and radon. It discusses the prospect of using the novel 225Ac-prostate-specific membrane antigen ligand-617 ligand as a therapeutic agent for prostate cancer. It presents a new treatment system that we developed, α-Radiorespiro-Rn, which seems to be extremely effective in treating cancer.
15 citations
References
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TL;DR: This text is a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA.
Abstract: The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.
1,359 citations
TL;DR: The results suggest that the various forms of non-radiation DNA damage in tissues far outweigh corresponding DNA damage from low-dose radiation exposure at the level of, and well above, background radiation, suggesting the LNT hypothesis is invalid for complex adaptive systems such as mammalian organisms.
Abstract: Ionizing radiation (IR) causes damage to DNA that is apparently proportional to absorbed dose. The incidence of radiation-induced cancer in humans unequivocally rises with the value of absorbed doses above about 300 mGy, in a seemingly linear fashion. Extrapolation of this linear correlation down to zero-dose constitutes the linear-no-threshold (LNT) hypothesis of radiation-induced cancer incidence. The corresponding dose-risk correlation, however, is questionable at doses lower than 300 mGy. Non-radiation induced DNA damage and, in consequence, oncogenic transformation in non-irradiated cells arises from a variety of sources, mainly from weak endogenous carcinogens such as reactive oxygen species (ROS) as well as from micronutrient deficiencies and environmental toxins. In order to relate the low probability of radiation-induced cancer to the relatively high incidence of non-radiation carcinogenesis, especially at low-dose irradiation, the quantitative and qualitative differences between the DNA damages from non-radiation and radiation sources need to be addressed and put into context of physiological mechanisms of cellular protection. This paper summarizes a co-operative approach by the authors to answer the questions on the quantitative and qualitative DNA damages from non-radiation sources, largely endogenous ROS, and following exposure to low doses of IR. The analysis relies on published data and justified assumptions and considers the physiological capacity of mammalian cells to protect themselves constantly by preventing and repairing DNA damage. Furthermore, damaged cells are susceptible to removal by apoptosis or the immune system. The results suggest that the various forms of non-radiation DNA damage in tissues far outweigh corresponding DNA damage from low-dose radiation exposure at the level of, and well above, background radiation. These data are examined within the context of low-dose radiation induction of cellular signaling that may stimulate cellular protection systems over hours to weeks against accumulation of DNA damage. The particular focus is the hypothesis that these enhanced and persisting protective responses reduce the steady state level of non-radiation DNA damage, thereby reducing deleterious outcomes such as cancer and aging. The emerging model urgently needs rigorous experimental testing, since it suggests, importantly, that the LNT hypothesis is invalid for complex adaptive systems such as mammalian organisms.
180 citations
TL;DR: Populations living in high background radiation areas and nuclear workers with increased radiation exposure show lower mortality and decreased cancer mortality than the corresponding populations living in low background radiation Areas andnuclear workers without increased radiation Exposure.
Abstract: Antimutagenic DNA damage-control is the central component of the homeostatic control essential for survival. Over eons of time, this complex DNA damage-control system evolved to control the vast number of DNA alterations produced by reactive oxygen species (ROS), generated principally by leakage of free radicals from mitochondrial metabolism of oxygen. Aging, mortality and cancer mortality are generally accepted to be associated with stem cell accumulation of permanent alterations of DNA, i.e., the accumulation of mutations. In a young adult, living in a low LET background of 0.1 cGy/y, the antimutagenic system of prevention, repair and removal of DNA alterations reduces about one million DNA alterations/cell/d to about one mutation/cell/d. DNA alterations from background radiation produce about one additional mutation per 10 million cells/d. As mutations accumulate and gradually degrade the antimutagenic system, aging progresses at an increasing rate, mortality increases correspondingly, and cancer increases at about the fourth power of age. During the past three decades, genomic, cellular, animal and human data have shown that low-dose ionizing radiation, including acute doses up to 30 cGy, stimulates each component of the homeostatic antimutagenic control system of antioxidant prevention, enzymatic repair, and immunologic and apoptotic removal of DNA alterations. On the other hand, high-dose ionizing radiation suppresses each of these antimutagenic protective components. Populations living in high background radiation areas and nuclear workers with increased radiation exposure show lower mortality and decreased cancer mortality than the corresponding populations living in low background radiation areas and nuclear workers without increased radiation exposure. Both studies of cancer in animals and clinical trials of patients with cancer also show, with high statistical confidence, the beneficial effects of low-dose radiation.
74 citations
"Commentary on Inhaled (239)PUO2 in ..." refers background in this paper
...Pollycove (2007) has summarized the rationale and radiobiological basis of low-dose irradiation for the prevention and therapy of cancer....
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TL;DR: A reduction of cellular thymidine kinase activity may be regarded as an instance of radiation hormesis in the sense that such a compensatory response to the stimulus of irradiation may confer protection against a repeated increase in free radical concentration whether by renewed radiation exposure or by metabolism in general.
Abstract: Non-specific generation of intracellular free radicals in excess of normal levels, e.g. by the acute radiation absorption event in cells, has led to a delayed and temporary inhibition of thymidine kinase. The enzyme activity reaches a minimum at 4 h even after a low-level exposure with full recovery soon thereafter. This process appears to represent a biochemical response to an initial physical event, but must be distinguished from the response of the DNA repair enzyme system. A reduction of cellular thymidine kinase activity is expected to cause a temporary reduction of DNA synthesis and may be of advantage to the cell. Such a response may be regarded as an instance of radiation hormesis in the sense that such a compensatory response to the stimulus of irradiation may confer protection against a repeated increase in free radical concentration whether by renewed radiation exposure or by metabolism in general. An improvement of the efficiency of repair or an increased level of free radical detoxification should be of benefit to both the individual cell and to the organism as a whole.
73 citations
"Commentary on Inhaled (239)PUO2 in ..." refers background in this paper
...The biological phenomenon that results from adaptive protection is radiation hormesis (Feinendegen et al. 1987, 2011, 2013)....
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01 Jan 2012
TL;DR: Adaptive protection preventing only about 2–3 % of endogenous lifetime cancer risk would fully balance a calculated-induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect.
Abstract: Ionizing radiation primarily perturbs the basic molecular level proportional to dose, with potential damage propagation to higher levels: cells, tissues, organs, and whole body There are three types of defenses against damage propagation These operate deterministically and below a certain impact threshold there is no propagation Physical static defenses precede metabolic-dynamic defenses acting immediately: scavenging of toxins;—molecular repair, especially of DNA;—removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses,—followed by replacement of lost elements Another metabolic-dynamic defense arises delayed by up-regulating immediately operating defense mechanisms Some of these adaptive protections may last beyond a year and all create temporary protection against renewed potentially toxic impacts also from nonradiogenic endogenous sources Adaptive protections have a maximum after single tissue absorbed doses around 100–200 mSv and disappear with higher doses Low dose-rates initiate maximum protection likely at lower cell doses delivered repetitively at certain time intervals Adaptive protection preventing only about 2–3 % of endogenous lifetime cancer risk would fully balance a calculated-induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect Low-dose-risk modeling must recognize up-regulation of protection
66 citations
"Commentary on Inhaled (239)PUO2 in ..." refers background in this paper
...Radiation hormesis theory (Feinendegen et al. 2013) is based on the following biological facts:...
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...The biological phenomenon that results from adaptive protection is radiation hormesis (Feinendegen et al. 1987, 2011, 2013)....
[...]
...Radiation hormesis theory (Feinendegen et al. 2013) is based on the following biological facts: 1....
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