Journal Issue:
Dose-Response: An International Journal: Volume 7, Issue 4

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2009-31-12
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PERSPECTIVE ON THE USE OF LNT FOR RADIATION PROTECTION AND RISK ASSESSMENT BY THE U.S. ENVIRONMENTAL PROTECTION AGENCY
(2009-12-01) Puskin, Jerome S
The U.S. Environmental Protection Agency (EPA) bases its risk assessments, regulatory limits, and nonregulatory guidelines for population exposures to low level ionizing radiation on the linear no-threshold (LNT) hypothesis, which assumes that the risk of cancer due to a low dose exposure is proportional to dose, with no threshold. The use of LNT for radiation protection purposes has been repeatedly endorsed by authoritative scientific advisory bodies, including the National Academy of Sciences’ BEIR Committees, whose recommendations form a primary basis of EPA’s risk assessment methodology. Although recent radiobiological findings indicate novel damage and repair processes at low doses, LNT is supported by data from both epidemiology and radiobiology. Given the current state of the science, the consensus positions of key scientific and governmental bodies, as well as the conservatism and calculational convenience of the LNT assumption, it is unlikely that EPA will modify this approach in the near future.
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INVESTIGATION OF NON-LINEAR ADAPTIVE RESPONSES AND SPLIT DOSE RECOVERY INDUCED BY IONIZING RADIATION IN THREE HUMAN EPITHELIAL DERIVED CELL LINES
(2009-12-01) Ryan, Lorna A; Seymour, Colin B; Mothersill, Carmel E
Two almost completely exclusive fields in radiobiology deal with splitting doses of radiation and comparing the effect to a similar total dose given in one exposure. In radiotherapy, dose “fractionation” is used to “spare” normal tissue and in the low dose field, the adaptive response is well documented as a phenomenon where a small “priming” dose administered before the larger “challenge “ dose reduces the effect of the large dose. There have been very few studies where these fields overlap, thus it is not possible to ascertain whether common or distinct mechanisms underlie both phenomena but this is certainly an interesting question and relevant to our understanding of high and low dose radiobiology. This paper presents data for three human cell lines with varying p53 status and radiation responses, treated at a range of times between first and second dose and for 3 different first doses (0.1, 0.5 and 2Gy). The data show that time between doses is critical. Protective (adaptive) effects were seen in each cell line but most prominently in the malignant HT 29 cell line. Surprisingly none of the cell lines showed pronounced split dose recovery. This suggests different mechanisms may underlie the two phenomena.
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THE HORMETIC MORPHOGEN THEORY OF CURVATURE AND THE MORPHOGENESIS AND PATHOLOGY OF TUBULAR AND OTHER CURVED STRUCTURES
(2009-12-01) Fosslien, Egil
In vitro, morphogens such as transforming growth factor (TGF)-β can up-and downregulate cell growth at low and high concentrations respectively, i.e. they behave like hormetic agents. The hormetic morphogen theory of curvature proposes that in vivo tissue gradients of such morphogens secreted by source cells determine the fate of cells within their gradient fields (field cells) and that morphogen-induced amplitude modulation of field cell mitochondrial adenosine triphosphate (ATP) generation controls field cell growth along the morphogen gradients: At the high concentration end of gradients, field cell ATP generation and field cell growth is reduced. With declining concentrations along the rest of the gradients field cell ATP and growth is progressively less reduced until an equidyne point is reached, beyond which ATP generation and growth gradually increases. Thus, the differential growth rates along the gradients curve the tissue. Apoptosis at very high morphogen concentrations enables lumen and cavity formation of tubular, spherical, cystic, domed, and other curved biological structures. The morphogen concentration, the gradient slope and the hormesis responses of field cells determine the curvature of such structures during developmental morphogenesis, tissue remodeling and repair of injury. Aberrant hormetic morphogen signaling is associated with developmental abnormalities, vascular diseases, and tumor formation.
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CALCULATING HEMATOPOIETIC-MODE-LETHALITY RISK AVOIDANCE ASSOCIATED WITH RADIONUCLIDE DECORPORATION COUNTERMEASURES RELATED TO A RADIOLOGICAL TERRORISM INCIDENT
(2009-12-01) Scott, Bobby R
This paper provides theoretical health-risk-assessment tools that are designed to facilitate planning for and managing radiological terrorism incidents that involve ingestion exposure to bone-seeking radionuclides (e.g., radiostrontium nuclides). The focus is on evaluating lethality risk avoidance (RAV; i.e., the decrease in risk) that is associated with radionuclide decorporation countermeasures employed to remove ingested bone-seeking beta and/or gamma-emitting radionuclides from the body. To illustrate the application of tools presented, hypothetical radiostrontium decorporation scenarios were considered that involved evaluating the hematopoietic-mode-lethality RAV. For evaluating the efficacy of specific decorporation countermeasures, the lethality risk avoidance proportion (RAP; which is the RAV divided by the total lethality risk in the absence of protective countermeasures) is introduced. The lethality RAP is expected to be a useful tool for designing optimal radionuclide decorporation schemes and for identifying green, yellow and red dose-rate zones. For the green zone, essentially all of the lethality risk is expected to be avoided (RAP = 1) as a consequence of the radionuclide decorporation scheme used. For the yellow zone, some but not all of the lethality risk is expected to be avoided. For the red zone, none of the lethality risk (which equals 1) is expected to be avoided.
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BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY
(2009-12-01) Huang, Ying-Ying; Chen, Aaron C-H; Carroll, James D; Hamblin, Michael R
The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.
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