Evidence Of Hormesis Research Articles

A gift from parent to offspring: transgenerational hormesis.

Hormesis is a biological phenomenon characterized by opposite effects between low and high doses of stresses that can result in stimulatory and adaptive benefits to individuals within a population. While evidence of hormesis is well established, two recent studies (Nogueira et al., Belz and Sinkkonen) suggest that hormesis can also offer transgenerational benefit.

Evidence of hormesis on human neuronal SK-N-BE cells treated with sodium arsenate: impact at the mitochondrial level.

Exposure of human neuronal SK-N-BE cells to sodium arsenate (AsV 0.1-400μM; 48h) induced a biphasic toxic effect evoking hormesis. Indeed, at low concentrations, AsV stimulates cell proliferation visualized by phase contrast microscopy, whereas at high concentrations, an induction of cell death associated with a loss of cell adhesion was observed. These side effects were confirmed with crystal violet test, cell cycle analysis, evaluation of the percentage of Ki67 positive cells, and staining with propidium iodide. The impact of AsV on mitochondrial functions, which was determined by the MTT assay, the measurement of mitochondrial transmembrane potential with DiOC6(3), and the rate of mitochondrial ATP, also support an hormesis process. In addition, in the presence of high concentrations of AsV, a significant decrease of the protein expression of OXPHOS complexes of the respiratory chain was observed by western blot supporting that AsV-induced cell death is associated with mitochondrial alterations. Therefore, there are some evidences of hormesis on AsV-treated SK-N-BE cells, and at high concentrations, the mitochondria are a target of toxicity induced by AsV.

Evidence of hormesis on human neuronal SK-N-BE cells treated with sodium arsenate: Impact at the mitochondrial level

Evidence of hormesis on human neuronal SK-N-BE cells treated with sodium arsenate: Impact at the mitochondrial level

A Meta-Analysis of Evidence for Hormesis in Animal Radiation Carcinogenesis, Including a Discussion of Potential Pitfalls in Statistical Analyses to Detect Hormesis

A database containing 800 datasets on the incidence of specific tumor types from 262 radiation carcinogenicity experiments identified in a comprehensive literature search through September 2000 was analyzed for evidence of hormesis. This database includes lifetime studies of tumorigenic responses in mice, rats, and dogs to exposures to alpha, beta, gamma, neutron, or x-ray radiation. A J-shaped dose response, in the form of a significant decreased response at some low dose followed by a significant increased response at a higher dose, was found in only four datasets from three experiments. Three of these datasets involved the same control animals and two also shared dosed animals; the J shape in the fourth dataset appeared to be the result of an outlier within an otherwise monotonic dose response. A meta-analysis was conducted to determine whether there was an excess of dose groups with decreases in tumor response below that in controls at doses below no-observed-effect levels (NOELs) in individual datasets. Because the probability of a decreased response is generally not equal to the probability of an increased response even in the null case, the meta-analysis focused on comparing the number of statistically significant diminished responses to the number expected, assuming no dose effect below the NOEL. Only 54 dose groups out of the total of 2579 in the database had doses below the dataset-specific NOEL and that satisfied an a priori criterion for sufficient power to detect a reduced response. Among these 54, a liberal criterion for defining a significant decreases identified 15 such decreases, versus 54 × 0.2 = 10.8 expected. The excess in significant reductions was accounted for almost entirely by the excess from neutron experiments (10 observed, 6.2 expected). Nine of these 10 dose groups involved only 2 distinct control groups, and 2 pairs from the 10 even shared dosed animals. Given this high degree of overlap, this small excess did not appear remarkable, although the overlap prevented a formal statistical analysis. A comprehensive post hoc evaluation using a range of NOEL definitions and alternative ways of restricting the data entering the analysis did not produce materially different results. A second meta-analysis found that, in every possible low dose range ([0, d] for every dose, d) of each of the radiation types, the number of dose groups with significantly increased tumorigenic responses was either close to or exceeded the number showing significantly reduced responses. This meta-analysis was considered to be the more definitive one. Not only did it take dose into account by looking for consistent evidence of hormesis throughout defined low-dose ranges, it was also potentially less susceptible to limitations in experimental protocols that would cause individual animals to respond in a non-independent fashion. Overall, this study found little evidence in a comprehensive animal radiation database to support the hormesis hypothesis. However, the ability of the database to detect a hormetic effect was limited both by the small number of dose groups with doses below the range where positive effects have been found in epidemiological studies (≤ 0.1 Gy) and by the limited power of many of these dose groups for detecting a decrease in response.

An illusion of hormesis in the Ames test: Statistical significance is not equivalent to biological significance

A recent report (Calabrese et al., Mutat. Res. 726 (2011) 91–97) concluded that an analysis of Ames test mutagenicity data provides evidence of hormesis in mutagenicity dose–response relationships. An examination of the data used in this study and the conclusions regarding hormesis reveal a number of concerns regarding the analyses and possible misinterpretations of the Salmonella data. The claim of hormesis is based on test data from the National Toxicology Program using Salmonella strain TA100. Approximately half of the chemicals regarded as hormetic, and the majority of the specific dose–responses identified as hormetic, were actually nonmutagenic. We conclude that the data provide no evidence of hormetic effects. The Ames test is an excellent measure of bacterial mutagenicity, but the numbers of revertant (mutant) colonies on the plate are the result of a complex interaction between mutagenicity and toxicity, which renders the test inappropriate for demonstrating hormesis in bacterial mutagenicity experiments.

Extracts from seaweeds can promote fungal growth.

Hormesis is the stimulation of a biological response at low concentrations of an inhibitor. Ethanolic extracts were made using Osmundaria serrata (Suhr) R. E. Norris and Stypopodium zonale (Lamouroux) Papenfuss from the East coast of South Africa. Two plant pathogens (Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. and Rhizoctonia solani Kühn) were used as test organisms in bioassays. Serial dilutions of macroalgal extracts were tested by the pour plate technique. Both growth inhibitory and promotory responses were observed. The hormetic response was observed in both the fungi when grown on low dilutions of ethanol and the O. serrata extract, and when R. solani was grown on the S. zonale extract. This study provides more evidence of hormesis in macroalgal products and the phenomenon is discussed in relation to its possible cause and significance in the application of seaweed extracts.

The Concept of Hormesis in Developmental Toxicology

Animal bioassay experiments are frequently conducted to assess the toxicity of chemicals on the developing fetus. Experiments are normally conducted at dosage levels that are much higher than human exposure levels to elicit the toxic reproductive effect of the chemical in a limited number of litters. Recently there has been much discussion on the fact that some chemicals may have beneficial effects at low doses and become toxic at high doses. This concept, known as chemical hormesis, has been the focus of attention in many investigations. Here, we consider the prevalence of hormesis in developmental toxicology and show that current design of developmental toxicity testing does not accommodate the study of hormesis. If it can be proved that some developmental toxicants may have stimulatory low dose effects, then design and analysis of developmental toxicity experiments need to be revised by the scientific community and the regulatory agencies. Using a thorough analysis of an experimental data set, we further demonstrate that in order to establish the possible hormetic effects of a chemical in reproduction, often a multiple replication of the experiment may be necessary to examine such effects. Using a trend test, we illustrate that while it is possible that one replicate of a developmental toxicity experiment with a known teratogen shows strong evidence of hormesis, other replicates may show no sign of beneficial effects at low doses.

Can the concept of hormesis Be generalized to carcinogenesis?

The concept of hormesis (i.e., low-dose stimulation/high-dose inhibition) has been shown to be widely generalizable with respect to chemical class, animal model, gender, and biological end point. The public health implication of this lack of linearity in the low-dose area of the dose-response curve raises the question of whether low doses of carcinogens will reduce cancer risk. Articles relating to the process of carcinogenesis (i.e., initiation, promotion, tumor development, and progression) were obtained from a recently developed chemical hormesis database and evaluated for their evidence of hormesis. Numerous examples in well-designed studies indicate that U- or J-shaped dose-response relationships exist with respect to various biomarkers of carcinogenesis in different animal models of both sexes. Examples of such J-shaped dose-response relationships in each stage of the process of carcinogenesis were selected for detailed toxicological examination. These results have important implications for both the hazard assessment of carcinogens and cancer risk assessment procedures.

FACTORS CONTROLLING THE RESPONSE OF FIELD CROPS TO VERY LOW DOSES OF GAMMA IRRADIATION OF THE SEED

Stimulation of growth by very low doses of ionizing radiation, or hormesis, is a widely documented phenomenon. The biochemical mechanisms are unclear and the phenomenon is sporadic, controlled by factors as yet only poorly understood. Our study addressed factors reported to control the growth response of plants to seed irradiation. A growth chamber experiment compared the effects of four radiation sources on three crop species. Early emergence of flax (Linum usitatissimum) and early growth of wheat (Triticum aestivum) and barley (Hordeum vulgare) were increased by irradiation. These effects did not vary as a function of the photon-energy or dose-rate of the sources. Three field experiments were conducted where various cultivars and seed lots of wheat were irradiated at doses of 0.5–50 Gy using Cobalt-60. Early emergence was significantly accelerated in 7 of 18 seed lots. Grain yields were significantly increased in five cases for Neepawa or Glenlea cultivars, but were significantly decreased in nine other cases. The effects were not consistently related to measured seed lot characteristics, manipulation of the seed moisture content prior to irradiation, or the post-seeding environment as varied by delayed planting. In conclusion, there was some evidence of hormesis in emergence and early growth, but these effects did not persist to yield a benefit at harvest.Key words: Hormesis, stimulation, wheat, barley, flax, irradiation