Hormesis: Improving Predictions in the Low-Dose Zone
ABSTRACT This chapter explores the historical foundations of hormesis, including the underlying reasons for its marginalization during most of the twentieth century and factors that are contributing to its resurgence and acceptance within the toxicological and pharmacological communities. Special consideration is given to the quantitative features of the hormetic dose response, as well as its capacity for generalization. Based on subsequent comparisons with other leading dose-response models, the hormesis dose response consistently provides more accurate predictions in the below threshold zone. It is expected that the hormetic dose response will become progressively more useful to the fields of toxicology, pharmacology, risk assessment, and the life sciences in general, especially where low-dose effects are of interest.
- SourceAvailable from: Alice Rotini[Show abstract] [Hide abstract]
ABSTRACT: Hormesis is a biphasic dose-response relationship, occurring when low concentrations of toxic agents elicit apparent improvements. In this work, the ability of sub-inhibitory concentrations of Tetracycline to induce hormetic response in a model organism was investigated. To this aim a reference strain of Escherichia coli, MG1655, was exposed to six decreasing doses of Tetracycline (between 0.12 and 0.00375 μg/ml), much lower than the Minimal Inhibitory Concentration (4 μg/ml). An hormetic increase was observed at the intermediate concentrations (0.015-0.03 μg/ml) of the tested range. The Colony Forming Unit number, indeed, rose up to 141% and 121% as compared to the control. At the highest (0.12 μg/ml) and lowest (0.00375 μg/ml) concentrations a slight decrease in CFU number was found. Results demonstrated that, in Escherichia coli, low concentrations of Tetracycline bias the bacterial numerical increase through a hormetic response; the dose-response curve describing this numerical increase is an U-inverted curve. Furthermore, these data confirm that hormesis is common to many - if not all - living systems, including bacteria; they underline the relevance of a deepened knowledge of both the effects and the possible consequences of exposure to low doses of contaminants.Dose-Response 01/2013; 11(4):550-557. DOI:10.2203/dose-response.13-002.Migliore · 1.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: There is a great deal of uncertainty on how low (≤0.1 Gy) doses of ionizing radiation (IR) affect human cells, partly due to a lack of suitable experimental model systems for such studies. The uncertainties arising from low-dose IR human data undermine practical societal needs to predict health risks emerging from diagnostic medical tests' radiation, natural background radiation, and environmental radiological accidents. To eliminate a variability associated with remarkable differences in radioresponses of hundreds of differentiated cell types, we established a novel, human embryonic stem cell (hESC)-based model to examine the radiobiological effects in human cells. Our aim is to comprehensively elucidate the gene expression changes in a panel of various hESC lines following low IR doses of 0.01; 0.05; 0.1 Gy; and, as a reference, relatively high dose of 1 Gy of IR. Here, we examined the dynamics of transcriptional changes of well-established IR-responsive set of genes, including CDKN1A, GADD45A, etc. at 2 and 16 h post-IR, representing "early" and "late" radioresponses of hESCs. Our findings suggest the temporal- and hESC line-dependence of stress gene radioresponses with no statistically significant evidence for a linear dose-response relationship within the lowest doses of IR exposures.International Journal of Molecular Sciences 01/2013; 15(1):588-604. DOI:10.3390/ijms15010588 · 2.34 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed.Journal of Environmental Radioactivity 05/2013; 133. DOI:10.1016/j.jenvrad.2013.04.002 · 3.57 Impact Factor