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.
"Another interesting point is that epigenetics allows hormetic effects to be considered. In the U-shaped hormetic dose–response curves, the same substance can have both stimulatory and inhibitory effects depending upon concentration.75,76 The menopause then resets the risk, as it were. "
[Show abstract][Hide abstract] ABSTRACT: This discussion paper seeks to provoke thoughts about cancer research in general, and why breast cancer in particular is not yet "curable". It asks the question - are we looking at the disease in the right way? Should we regard cancer as a progressive state, which is part of aging? Should we tailor treatment to "reset" the system or slow progression rather than try using toxic and aggressive therapy to kill every cancer cell (and sometimes also the patient)? The thesis is presented that we need to revisit our fundamental beliefs about the disease and then ask why we cling to beliefs that clearly are no longer valid. The paper also questions the role of ethics boards in hampering research and discusses the concept that breast cancer is an industry with vested interests involving profiteering by preventive, diagnostic, and therapeutic players. Finally, the paper suggests some ways forward based on emerging concepts in system biology and epigenetics.
Breast Cancer: Targets and Therapy 12/2013; 5:111-9. DOI:10.2147/BCTT.S44399
"All of these findings point to superoxide anions as a guilty party in the loss of cellular homoeostasis that underlies ageing and to low levels of hydrogen peroxide as the 'sheriff' that keeps superoxide anions in check. The critical role of hydrogen peroxide in policing levels of superoxide anions conforms to current concepts of a phenomenon called hormesis (Calabrese, 2012). However, the results of some studies suggest that not all superoxide anions are bad guys that need to be restrained by oxidative stress defences – similar to hydrogen peroxide, superoxide anions are also capable of enhancing lifespan (Fig. 1). "
[Show abstract][Hide abstract] ABSTRACT: For more than 50 years the Free Radical Theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis. This article is protected by copyright. All rights reserved.
FEMS Yeast Research 08/2013; 14(1). DOI:10.1111/1567-1364.12070 · 2.82 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 · 2.86 Impact Factor
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