Showing papers in "Dose-response in 2015"
TL;DR: The utility of coordinating global sensing of environmental contaminants efforts through integration of environmental monitoring and specimen banking to identify regions for implementation of more robust environmental assessment and management programs is highlighted.
Abstract: Because bisphenol A (BPA) is a high production volume chemical, we examined over 500 peer-reviewed studies to understand its global distribution in effluent discharges, surface waters, sewage sludge, biosolids, sediments, soils, air, wildlife, and humans. Bisphenol A was largely reported from urban ecosystems in Asia, Europe, and North America; unfortunately, information was lacking from large geographic areas, megacities, and developing countries. When sufficient data were available, probabilistic hazard assessments were performed to understand global environmental quality concerns. Exceedances of Canadian Predicted No Effect Concentrations for aquatic life were >50% for effluents in Asia, Europe, and North America but as high as 80% for surface water reports from Asia. Similarly, maximum concentrations of BPA in sediments from Asia were higher than Europe. Concentrations of BPA in wildlife, mostly for fish, ranged from 0.2 to 13 000 ng/g. We observed 60% and 40% exceedences of median levels by the US Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey in Europe and Asia, respectively. These findings highlight the utility of coordinating global sensing of environmental contaminants efforts through integration of environmental monitoring and specimen banking to identify regions for implementation of more robust environmental assessment and management programs.
508 citations
TL;DR: Taking into account that the incidence and/or prevalence of health problems associated with endocrine disruption have increased worldwide, the goal of the present review is to give an overview of the many mechanisms of BPA action in order to decipher whether different mechanisms are at the root of the effect of low dose of B PA on endocrine system.
Abstract: Bisphenol A (BPA) exposure has been associated with serious endocrine-disrupting effects in humans and wildlife. Toxicological and epidemiological studies evidenced that BPA increases body mass index and disrupts normal cardiovascular physiology by interfering with endogenous hormones in rodents, nonhuman primates, and cell culture test systems. The BPA concentration derived from these experiments were used by government regulatory agencies to determine the safe exposure levels of BPA in humans. However, accumulating literature in vivo and in vitro indicate that at concentrations lower than that reported in toxicological studies, BPA could elicit a different endocrine-disrupting capacity. To further complicate this picture, BPA effects rely on several and diverse mechanisms that converge upon endocrine and reproductive systems. If all or just few of these mechanisms concur to the endocrine-disrupting potential of low doses of BPA is at present still unclear. Thus, taking into account that the incidence and/or prevalence of health problems associated with endocrine disruption have increased worldwide, the goal of the present review is to give an overview of the many mechanisms of BPA action in order to decipher whether different mechanisms are at the root of the effect of low dose of BPA on endocrine system.
272 citations
TL;DR: In this article, the authors present an overview of available information on the effects of BPA on aquatic vertebrates and invertebrates to provide a general scenario and to suggest future developments toward more comprehensive approaches useful for aquatic species protection.
Abstract: Research on bisphenol A (BPA) as an environmental contaminant has now major regulatory implications toward the ecosystem health, and hence it is incumbent on scientists to do their research to the highest standards possible, in order that the most appropriate decisions are made to mitigate the impacts to aquatic wildlife. However, the contribution given so far appears rather fragmented. The present overview aims to collect available information on the effects of BPA on aquatic vertebrates and invertebrates to provide a general scenario and to suggest future developments toward more comprehensive approaches useful for aquatic species protection.
146 citations
TL;DR: Comparison and Bayesian analysis of the published data shows that the linear no-threshold hypothesis does not likely explain the results of these recent studies, whereas they favor the model of threshold or hormesis.
Abstract: There are many places on the earth, where natural background radiation exposures are elevated significantly above about 2.5 mSv/year. The studies of health effects on populations living in such places are crucially important for understanding the impact of low doses of ionizing radiation. This article critically reviews some recent representative literature that addresses the likelihood of radiation-induced cancer and early childhood death in regions with high natural background radiation. The comparative and Bayesian analysis of the published data shows that the linear no-threshold hypothesis does not likely explain the results of these recent studies, whereas they favor the model of threshold or hormesis. Neither cancers nor early childhood deaths positively correlate with dose rates in regions with elevated natural background radiation.
71 citations
TL;DR: Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health.
Abstract: Brain development is an organized, but constantly adaptive, process in which genetic and epigenetic signals allow neurons to differentiate, to migrate, and to develop correct connections. Gender specific prenatal sex hormone milieu participates in the dimorphic development of many neuronal networks. Environmental cues may interfere with these developmental programs, producing adverse outcomes. Bisphenol A (BPA), an estrogenic/antiandrogenic endocrine disruptor widely diffused in the environment, produces adverse effects at levels below the acceptable daily intake. This review analyzes the recent literature on the consequences of perinatal exposure to BPA environmental doses on the development of a dimorphic brain. The BPA interference with the development and function of the neuroendocrine hypothalamus and of the nuclei controlling energy balance, and with the hippocampal memory processing is also discussed. The detrimental action of BPA appears complex, involving different hormonal and epigenetic pathways activated, often in a dimorphic way, within clearcut susceptibility windows. To date, discrepancies in experimental approaches and in related outcomes make unfeasible to translate the available information into clear dose-response models for human risk assessment. Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health.
66 citations
TL;DR: The present review will overview the most relevant findings that confirm the critical role of bisphenol-A, one of the most widespread EDCs, in the development of metabolic disorders.
Abstract: Obesity and type 2 diabetes mellitus (T2DM) are the most common metabolic disorders, with prevalence rates that are reaching epidemic proportions. Both are complex conditions affecting virtually all ages and with serious health consequences. The underlying cause of the problem is still puzzling, but both genetic and environmental factors including unhealthy diet, sedentary lifestyle, or the exposure to some environmental endocrine disrupting chemicals (EDCs) are thought to have a causal influence. In addition, the impact of early environment has recently emerged as an important factor responsible for the increased propensity to develop adult-onset metabolic disease. Suboptimal maternal nutrition during critical windows in fetal development is the most commonly studied factor affecting early programming of obesity and T2DM. In recent years, increasing experimental evidence shows that exposure to EDCs could also account for this phenomenon. In the present review, we will overview the most relevant findings that confirm the critical role of bisphenol-A, one of the most widespread EDCs, in the development of metabolic disorders.
53 citations
TL;DR: In vitro irradiation of Raw264.7 monocytic and the YAC-1 lymphoma cell lines at very low-dose rate of 4cGy shows a transient increase in production of both free radicals and nitric oxide with a transient adaptive response during at least two weeks after the beginning of the irradiation.
Abstract: We have previously shown a delay of death by lymphoma in SJL/J mice irradiated with continuous very low doses of ionizing radiation. In order to understand the mechanisms involved in this phenomenon, we have irradiated in vitro the Raw264.7 monocytic and the YAC-1 lymphoma cell lines at very low-dose rate of 4cGy.month(-1). We have observed a transient increase in production of both free radicals and nitric oxide with a transient adaptive response during at least two weeks after the beginning of the irradiation. The slight decrease of Ki67 proliferation index observed during the second and third weeks of YAC-1 cells culture under irradiation was not significant but consistent with the shift of the proliferation assay curves of YAC-1cells at these same durations of culture. These in vitro results were in good agreement with the slightly decrease under irradiation of Ki67 proliferative index evaluated on lymphomatous lymph nodes of SJL/J mice. A significant decrease of YAC-1 cells apoptotic rate under radiation appeared after 4 weeks of culture. Therefore very small doses of gamma-irradiation are able to modify the cellular response. The main observations did not last with increasing time under irradiation, suggesting a transient adaptation of cells or organisms to this level of irradiation.
48 citations
TL;DR: This review discusses recent studies that have identified several different factors that appear to initiate exercise preconditioning and summarizes the evidence for and against specific cellular factors in triggering exercise adaptations.
Abstract: Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling events that occur during exercise to "trigger" cardioprotection represent emerging paradigms. In this review, we discuss recent studies that have identified several different factors that appear to initiate exercise preconditioning. We summarize the evidence for and against specific cellular factors in triggering exercise adaptations and identify areas for future study.
43 citations
TL;DR: There are still many gaps in the knowledge of the relationship between actual BPA exposure and cardiometabolic risk and of the modalities of food intake exposure, all of which prevents sound judgments concerning the risks to human health.
Abstract: Bisphenol A (BPA), a known endocrine disruptor, is a food contaminant suspected of being a contributing factor to the present-day increase in obesity, diabetes, and cardiovascular disease. This issue is of increasing interest in the field of diabetes research and has become a matter of concern for regulatory agencies and food industries. Recently, the number of studies involving BPA has increased exponentially, but there are still many gaps in the knowledge of the relationship between actual BPA exposure and cardiometabolic risk and of the modalities of food intake exposure, all of which prevents sound judgments concerning the risks to human health. This review focuses on the association between human exposure to BPA and obesity, thyroid function, diabetes, insulin resistance, metabolic syndrome, cardiovascular diseases, and BPA content in food. Many cross-sectional studies support, sometimes contradictorily, an adverse effect of BPA exposure on obesity, diabetes, and cardiovascular diseases. Few prospective studies support an adverse effect of BPA exposure on such pathologies. Moreover, no intervention studies have been conducted to evaluate the causality of such associations. This is mainly due to lack of an appropriate database of BPA content in foods, thus hindering any estimation of the usual dietary BPA intake.
40 citations
TL;DR: These findings provide further evidence of the potential risks that developmental exposure to low doses of the endocrine disrupter BPA may pose to human health, with fetuses and infants being highly vulnerable.
Abstract: We review here our studies on early exposure to low doses of the estrogenic endocrine-disrupting chemical bisphenol A (BPA) on behavior and metabolism in CD-1 mice. Mice were exposed in utero from gestation day (GD) 11 to delivery (prenatal exposure) or via maternal milk from birth to postnatal day 7 (postnatal exposure) to 10 µg/kg body weight/d of BPA or no BPA (controls). Bisphenol A exposure resulted in long-term disruption of sexually dimorphic behaviors. Females exposed to BPA pre- and postnatally showed increased anxiety and behavioral profiles similar to control males. We also evaluated metabolic effects in prenatally exposed adult male offspring of dams fed (from GD 9 to 18) with BPA at doses ranging from 5 to 50 000 µg/kg/d. The males showed an age-related significant change in a number of metabolic indexes ranging from food intake to glucose regulation at BPA doses below the no observed adverse effect level (5000 µg/kg/d). Consistent with prior findings, low but not high BPA doses produced significant effects for many outcomes. These findings provide further evidence of the potential risks that developmental exposure to low doses of the endocrine disrupter BPA may pose to human health, with fetuses and infants being highly vulnerable.
31 citations
TL;DR: This paper critically examines claims that some authors claim that they now have direct epidemiological evidence of carcinogenic risks from medical imaging, and concludes that the evidence cited does not provide direct evidence of low-dose carcinogenicity.
Abstract: Several radiation-related professional societies have concluded that carcinogenic risks associated with doses below 50-100 mSv are either too small to be detected, or are nonexistent This is especially important in the context of doses from medical imaging Radiation exposure to the public from medical imaging procedures is rising around the world, primarily due to increased utilization of computed tomography Professional societies and advisory bodies consistently recommend against multiplying small doses by large populations to predict excess radiation-induced cancers, in large part because of the potential for sensational claims of health impacts which do not adequately take the associated uncertainties into account Nonetheless, numerous articles have predicted thousands of future cancers as a result of CT scanning, and this has generated considerable concern among patients and parents In addition, some authors claim that we now have direct epidemiological evidence of carcinogenic risks from medical imaging This paper critically examines such claims, and concludes that the evidence cited does not provide direct evidence of low-dose carcinogenicity These claims themselves have adverse public health impacts by frightening the public away from medically justified exams It is time for the medical and scientific communities to be more assertive in responding to sensational claims of health risks
TL;DR: Regression analysis revealed dependences of LP rate and GPX activity on traffic intensity in Betula pendula and T cordata were paradoxical effects and other regulatory mechanisms instead of GPX were activated which could control LP rate under middle- and high-level pollution.
Abstract: Hormesis and paradoxical effects are frequently found for different plant parameters. These phenomena were also observed for lipid peroxidation (LP) rate at environmental pollution. However, the role of antioxidant enzymes, particularly guaiacol peroxidases (GPX), in a nonmonotonic variation in the LP rate remains insufficiently explored. Therefore, dependence of GPX activity and LP rate in Betula pendula and Tilia cordata leaf on motor traffic pollution intensity was studied. Regression analysis revealed dependences of LP rate and GPX activity on traffic intensity. In B pendula, GPX activity enhanced significantly (up to 2.8 times relatively control) under increased traffic that induced biphasic paradoxical effect for LP rate. In the first phase, LP level increased in comparison with the control, and in the second phase, it was normalized by enhanced GPX activity. In T cordata, dependences of GPX activity and LP rate on traffic pollution were paradoxical effects. However, there was no connection between change of GPX activity and LP rate under middle- and high-level pollution: LP level reduced relatively the control or normalized even if GPX activity was lower than the control. This indicates that in T cordata, other regulatory mechanisms instead of GPX were activated which could control LP rate under middle- and high-level pollution.
TL;DR: A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis.
Abstract: The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis This paper shows that this claim is baseless The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 03 Sievert (Sv) and saturation level at about 15 Sv A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 25% per Sv, ie, an increase of cancer mortality from about 20% spontaneous mortality to about 225% per Sv, which is about half of the usually cited value The impact of the "neutron discrepancy problem" - the apparent difference between the calculated and measured values of neutron flux in Hiroshima - was studied and found to be marginal Major revision of the radiation risk assessment paradigm is required
TL;DR: Both LNT and hormesis can be integratively used for risk assessment purposes, and this integration defines the so-called “regulatory sweet spot.”
Abstract: On June 23, 2015, the US Nuclear Regulatory Commission (NRC) issued a formal notice in the Federal Register that it would consider whether “it should amend its ‘Standards for Protection Against Radiation’ regulations from the linear non-threshold (LNT) model of radiation protection to the hormesis model.” The present commentary supports this recommendation based on the (1) flawed and deceptive history of the adoption of LNT by the US National Academy of Sciences (NAS) in 1956; (2) the documented capacity of hormesis to make more accurate predictions of biological responses for diverse biological end points in the low-dose zone; (3) the occurrence of extensive hormetic data from the peer-reviewed biomedical literature that revealed hormetic responses are highly generalizable, being independent of biological model, end point measured, inducing agent, level of biological organization, and mechanism; and (4) the integration of hormesis and LNT models via a model uncertainty methodology that optimizes public h...
TL;DR: In vitro test models representative of the human feto–maternal interface and the effects of environmental chemicals with estrogen-like activity are described, mainly bisphenol A and para-nonylphenol, with a particular emphasis on the effects at low, nontoxic doses similar to concentrations commonly detected in the population.
Abstract: The identification of reproductive toxicants is a major scientific challenge for human health. Prenatal life is the most vulnerable and important time span of human development. For obvious ethical reasons, in vivo models cannot be used in human pregnancy, and animal models do not perfectly reflect human physiology. This review describes the in vitro test models representative of the human feto–maternal interface and the effects of environmental chemicals with estrogen-like activity, mainly bisphenol A and para-nonylphenol, with a particular emphasis on the effects at low, nontoxic doses similar to concentrations commonly detected in the population.
TL;DR: The hormetic responses of Lonicera japonica Thunb.
Abstract: The hormetic responses of Lonicera japonica Thunb. to cadmium (Cd) stress were investigated in a hydroponic experiment. The present results showed that root length and total biomass dry weight increased in comparison with the control at low concentrations Cd. The height of the plant exposed to 2.5 and 5 mg L(-1) Cd increased significantly by 11.9% and 12.8% relative to the control, and with the increase of Cd concentrations in the medium, plant height began to decrease. The responses of photosynthetic pigments contents and relative water content to Cd stress had a similar trend, which all showed significantly an inverted U-shaped dose-response curve and confirmed that the stimulatory effect of low concentrations Cd occurred in the plant. Furthermore, L. japonica, as a new Cd-hyperaccumulator, could be considered as a new plant model to study the underlying mechanisms of the hormesis.
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.
TL;DR: This in vivo animal investigation of PLDR for the treatment of recurrent cancers showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT.
Abstract: Objectives:This study investigates (1) local tumor control and (2) normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR) for recurrent lung cancer.Methods:For study 1, nude mice were i...
TL;DR: It is demonstrated that topoisomerase I inhibitor camptothecin (CPT), a potent anticancer agent, induced an obvious hormetic response in rat pheochromocytoma PC12 cells, and results suggest that the hormetic and neuroprotective effects of CPT at low doses were attributable, at least partially, to upregulated PI3K/Akt and Nrf2/HO-1 pathways.
Abstract: Hormetic response is an adaptive mechanism for a cell or organism surviving in an unfavorable environment. It has been an intriguing subject of researches covering a broad range of biological and medical disciplines, in which the underlying significance and molecular mechanisms are under intensive investigation. In the present study, we demonstrated that topoisomerase I inhibitor camptothecin (CPT), a potent anticancer agent, induced an obvious hormetic response in rat pheochromocytoma PC12 cells. Camptothecin inhibited PC12 cell growth at relative high doses as generally acknowledged while stimulated the cell growth by as much as 39% at low doses. Moreover, low doses of CPT protected the cells from hydrogen peroxide (H2O2)-induced cell death. Phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were reported playing pivotal roles in protecting cells from oxidative stress. We observed that these 2 pathways were upregulated by low doses of CPT, as evidenced by increased levels of phosphorylated PI3K, phosphorylated Akt, phosphorylated mammalian target of rapamycin, Nrf2, and HO-1; and abolishment of the growth-promoting and neuroprotective effects of CPT by LY294002, a PI3K inhibitor. These results suggest that the hormetic and neuroprotective effects of CPT at low doses on PC12 cells were attributable, at least partially, to upregulated PI3K/Akt and Nrf2/HO-1 pathways.
TL;DR: The discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information are outlined, yielding both value of information and flexibility associated with public choices.
Abstract: Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose-response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices.
TL;DR: The results in general followed the hormesis hypothesis, PCB 31 at lower concentrations exhibited beneficial effects on the growth of zebrafish by weight and length while higher concentrations revealed inhibitory effects.
Abstract: Hormesis is commonly defined as a beneficial or stimulatory effect caused by exposure to low doses of a chemical known to be toxic at high doses. Hormetic responses of food-supplied PCB 31 (2, 4', 5-Trichlorobiphenyl) was studied by using zebrafish (Danio rerio) growth as an end point. The results in general followed the hormesis hypothesis, PCB 31 at lower concentrations (0.042 μg/g and 0.084 μg/g) exhibited beneficial effects on the growth of zebrafish by weight and length while higher concentrations (10μg/g and 20μg/g) revealed inhibitory effects. The magnitude of stimulatory responses of zebrafish growth by weight and length at lower concentrations (0.01-0.084 μg/g) on days 14 and 21 were in the range 9.09-18.18%; 10-38.09% and 4-14.4%; 6.25-10.93%, respectively as compared to control. Growth and conditions indices also suggested that the zebrafish was healthier at lower concentrations as compared to those at higher concentrations. The results of the present study will elaborate fish toxicological evaluation regarding the hormetic model.
TL;DR: Cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and the radiation dose range that is effective for different tissues in the same animal are examined.
Abstract: h The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to “as low as reasonably achievable” (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations.
TL;DR: The results suggest a complex interplay of various stress response pathways triggered by low radiation doses, with various low dose thresholds for different genes.
Abstract: Understanding the mechanisms producing low dose ionizing radiation specific biological effects represents one of the major challenges of radiation biology. Although experimental evidence does suggest that various molecular stress response pathways may be involved in the production of low dose effects, much of the detail of those mechanisms remains elusive. We hypothesized that the regulation of various stress response pathways upon irradiation may differ from one another in complex dose-response manners, causing the specific and subtle low dose radiation effects. In the present study, the transcription level of 22 genes involved in stress responses were analyzed using RT-qPCR in normal human fibroblasts exposed to a range of gamma-doses from 1 to 200 cGy. Using the alkali comet assay, we also measured the level of DNA damages in dose-response and time-course experiments. We found non-linear dose responses for the repair of DNA damage after exposure to gamma-radiation. Alterations in gene expression were also not linear with dose for several of the genes examined and did not follow a single pattern. Rather, several patterns could be seen. Our results suggest a complex interplay of various stress response pathways triggered by low radiation doses, with various low dose thresholds for different genes.
TL;DR: Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation, but TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect.
Abstract: h Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.
TL;DR: By significantly up-regulating catalase levels over the entire range of doses from 0.5 to 4 Gy, the inhibitor of Hsp90 exerted adaptive protection and modified the early radiation response of the human blood cells.
Abstract: Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone, involved in the folding, assembly, stabilization and activation of numerous proteins with unrelated amino acid sequences and functions. Geldanamycin (GA), a natural benzoquinone, can inhibit the chaperone activity of Hsp90. It has been shown that GA can produce superoxide anions and increase the intracellular oxidative stress, which, in addition to the direct inhibition of Hsp90, might also contribute to the modifying effects of the inhibitor on the early response in human mononuclear cells exposed to ionizing radiation. The present study shows that GA antagonizes the radiation-induced suppression on MnSOD and catalase, key enzymes of the radical scavenging systems. By significantly up-regulating catalase levels over the entire range of doses from 0.5 to 4 Gy, the inhibitor of Hsp90 exerted adaptive protection and modified the early radiation response of the human blood cells.
TL;DR: In most cases, the studied phenological indexes and seed production decreased monotonically in comparison with the control following an increase in traffic intensity, and only in 2010 and 2013, share of fallen leaves had hormesis and paradoxical effect accordingly.
Abstract: Various plant indexes are used or recommended for bioindication. However, the nonmonotonic dose-response dependences (hormesis and paradoxical effects) of these indexes are insufficiently explored upon exposure to pollution. We studied the dependences of these Betula pendula indexes on the intensity of motor traffic pollution. Regression analysis did not reveal any dependence of chlorophyll and carotenoid content on traffic intensity (in 2008 and 2010-2013). Lipid peroxidation rate had different versions of paradoxical effects in 2008 and 2010 to 2012 and increased in comparison with control under an increase in pollution level in 2013. In 2010 to 2012, all dose-response dependences for total protein and thiol group content were biphasic and multiphasic paradoxical effects. In 2013, an increase in traffic intensity induced a linear reduction in protein content and an increase in thiol group level in comparison with the control. In most cases, the studied phenological indexes and seed production decreased monotonically in comparison with the control following an increase in traffic intensity. Only in 2010 and 2013, share of fallen leaves had hormesis and paradoxical effect accordingly. Fluctuating asymmetry had a paradoxical effect and hormesis in 2008 and 2012, accordingly, and increased in comparison with the control under an increase in the level of pollution in 2010 to 2011.
TL;DR: The present overcautious attitude to radiological hazards should be corrected in order to mitigate the present suffering and to avoid such suffering in the future.
Abstract: The Chernobyl accident led to major human suffering caused by the evacuation and other counter-measures. However, the direct health consequences of the accident-related radiation exposures, besides the acute effects and small number of thyroid cancers, have not been observed. This absence is challenged by some influential groups affecting public policies who claim that the true extent of radiogenic health consequences is covered up. We consider such claims. The most conservative (in this case - overestimating) linear no-threshold hypothesis was used to calculate excess cancer expectations for cleanup workers, the population of the contaminated areas and the global population. Statistical estimations were performed to verify whether such expected excess was detectable. The calculated cancer excess for each group is much less than uncertainties in number of cancer cases in epidemiological studies. Therefore the absence of detected radiation carcinogenesis is in full correspondence with the most conservative a priori expectations. Regarding the cover-up claims, rational choice analysis was performed. Such analysis shows that these claims are ill-founded. The present overcautious attitude to radiological hazards should be corrected in order to mitigate the present suffering and to avoid such suffering in the future.
TL;DR: The US Environmental Protection Agency should consider raising its radon action level from 150 to at least 1000 Bq/m3, and the radon limit near the no observed adverse effects level (NOAEL) above which inhaled radon decay products begin to induce excess lung cancer mortality.
Abstract: Cohen’s lung cancer mortality data, from his test of the LNT theory, do not extend to the no observed adverse effects level (NOAEL) above which inhaled radon decay products begin to induce excess lung cancer mortality. Since there is concern about the level of radon in homes, it is important to set the radon limit near the NOAEL to avoid the risk of losing a health benefit. Assuming that dogs model humans, data from a study on inhaled plutonium dioxide particulates in dogs were assessed, and the NOAEL for radon-induced lung tumors was estimated to be about 2100 Bq/m3. The US Environmental Protection Agency should consider raising its radon action level from 150 to at least 1000 Bq/m3.
TL;DR: 18F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.
Abstract: The biological effects of exposure to radioactive fluorodeoxyglucose ((18)F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo (18)F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of (18)F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of (18)F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual's radiation response. In summary, the results of this study indicate(18)F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.
TL;DR: The methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR, and exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals.
Abstract: The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.