Hormesis is any kind of biphasic dose-response when low doses of some agents are beneficial while higher doses are detrimental. Radiation hormesis is the most thoroughly investigated among all hormesis-like phenomena, in particular in biogerontology. In this review, we aimed to summarize research evidence supporting hormesis through exposure to low-dose ionizing radiation (LDIR). Radiation-induced longevity hormesis has been repeatedly reported in invertebrate models such as C. elegans, Drosophila and flour beetles and in vertebrate models including guinea pigs, mice and rabbits. On the contrary, suppressing natural background radiation was repeatedly found to cause detrimental effects in protozoa, bacteria and flies. We also discussed here the possibility of clinical use of LDIR, predominantly for age-related disorders, e.g., Alzheimer's disease, for which no remedies are available. There is accumulating evidence that LDIR, such as those commonly used in X-ray imaging including computer tomography, might act as a hormetin. Of course, caution should be exercised when introducing new medical practices, and LDIR therapy is no exception. However, due to the low average residual life expectancy in old patients, the short-term benefits of such interventions (e.g., potential therapeutic effect against dementia) may outweigh their hypothetical delayed risks (e.g., cancer). We argue here that assessment and clinical trials of LDIR treatments should be given priority bearing in mind the enormous economic, social and ethical implications of potentially-treatable, age-related disorders.

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Low-dose ionizing radiation as a hormetin: experimental observations and therapeutic perspective for age-related disorders

Juvenile rainbow trout ( Oncorhynchus mykiss ) were subjected to a 2-day radioactive pulse of 110m Ag at 11.9 μg/l (as AgNO 3 ), followed by a 19-day post-tracer exposure to non-radioactive Ag(I) (3.8 μg/l). The distribution of 110m Ag in the gills, liver, intestine, kidney, brain and remaining carcass was investigated over a 19-day post-tracer period. Initially, the intestine contained the highest proportion of the 110m Ag burden (34%), however, by day 8, less than 5% of the total radioactivity remained in this tissue. The majority of the 110m Ag eliminated from the intestine appeared to distribute to the liver. Eventually, the 110m Ag content in the liver accounted for as much as 65% of the total radioactivity in the fish. Apart from the liver and intestine, only the gills and carcass contained any appreciable amount (>5%) of the total body 110m Ag content. Liver and gill samples were fractionated using differential centrifugation techniques to discern the subcellular distribution of 110m Ag in these tissues. In the liver, the 110m Ag levels in the cytosolic fraction increased from 35% to 72% of the total cellular burden between days 8 and 19, respectively. The radioactive pulse in the gills was predominantly found in a membrane compartment termed the nuclear fraction (∼60% of the total). Little change was observed over time (day 8 to day 19) to the subcellular distribution of Ag in the gills. Using size-exclusion chromatography, most (∼70%) of the 110m Ag content in the liver cytosol eluted at a molecular weight characteristic of metallothionein. The cytosolic distribution of 110m Ag in gills was quite diffuse, occurring primarily in the heavy molecular weight fractions.

The distribution kinetics of waterborne silver-110m in juvenile rainbow trout.

Since the discovery of radioactivity more than a century ago, there are mountains of data about the effects of radiation on health. There is consensus that large doses cause harm. However, intense controversy exists regarding the health effects of low-level radiation. At the end of the 19th century and early in 20th century, it was generally believed that ionizing radiation has numerous beneficial effects. The low doses of radiation, mostly radium and X-rays, were considered to be medical marvels. It was claimed, for example, that blindness might be cured by X-rays. People went to spas to drink radioactive water or stayed for hours in caves to be irradiated by ionizing radiation. The “mild radium therapy” was widely used. This therapy involved the oral or parenteral administration of microgram quantities of radium and its daughter isotopes, often as cures for rheumatic diseases, hypertension, and metabolic disorders. Between 1925 and 1930 over 400,000 bottles of distilled water containing radium-226 and radium-228 were sold. It was advertised that some mixtures could treat over 150 diseases, especially lassitude and sexually impotence. The death of the Pittsburgh millionaire Eben M. Byers by radium poisoning in 1932 brought to an end to the era of “mild radium therapy” and alerted the public, and much of the medical profession, of the harmful effects of this therapy (for reviews see, e.g., Macklis 1990; Wolff 1992). Soon after the atomic bombing of Hiroshima and Nagasaki in 1945, the linear no-threshold (LNT) radiation risk model was derived. This model assumes that any exposure to ionizing radiation constitutes a risk for health and that risks increase proportionally with exposure. Primary, this model was offered as a prudent operational guideline. However, it acquired later the aura of fact even though no one has ever generated any evidence for it. In extrapolating from highto low-dose patterns of exposure, it neglects the fact that organisms have always been exposed to low

Irradiation and Hormesis

Bibliography: longevity, ageing and parental age effects in Drosophila (1907–86)

Since the discovery of radioactivity more than a century ago, there are mountains of data about the effects of radiation on health. There is consensus that large doses cause harm. However, intense controversy exists regarding the health effects of low-level radiation. At the end of the 19th century and early in 20th century, it was generally believed that ionizing radiation has numerous beneficial effects. The low doses of radiation, mostly radium and X-rays, were considered to be medical marvels. It was claimed, for example, that blindness might be cured by X-rays. People went to spas to drink radioactive water or stayed for hours in caves to be irradiated by ionizing radiation. The “mild radium therapy” was widely used. This therapy involved the oral or parenteral administration of microgram quantities of radium and its daughter isotopes, often as cures for rheumatic diseases, hypertension, and metabolic disorders. Between 1925 and 1930 over 400,000 bottles of distilled water containing radium-226 and radium-228 were sold. It was advertised that some mixtures could treat over 150 diseases, especially lassitude and sexually impotence. The death of the Pittsburgh millionaire Eben M. Byers by radium poisoning in 1932 brought to an end to the era of “mild radium therapy” and alerted the public, and much of the medical profession, of the harmful effects of this therapy (for reviews see, e.g., Macklis 1990; Wolff 1992). Soon after the atomic bombing of Hiroshima and Nagasaki in 1945, the linear no-threshold (LNT) radiation risk model was derived. This model assumes that any exposure to ionizing radiation constitutes a risk for health and that risks increase proportionally with exposure. Primary, this model was offered as a prudent operational guideline. However, it acquired later the aura of fact even though no one has ever generated any evidence for it. In extrapolating from high- to low-dose patterns of exposure, it neglects the fact that organisms have always been exposed to low

Radiation Hormesis: A Historical Introduction

The sparing effect of dose-fractionation was observed in adult male and femaleDrosophila melanogaster; 24-, 48-, 72-, and 96-h-old female flies, in general, show a higher recovery (increase in life-span) following dose-fractionation as compared to the males of the respective age. Recovery in 72-h-old females is maximal (31% increase in life-span) as against only 12% increase in the life span of the males.

A. Mohsin

Papers

The sparing effect of dose-fractionation in adultDrosophila