Radiation hormesis: Stimulatory effects of low doses ionizing radiation

Low to small doses of ionizing radiation conditionally show stimulatory effects in various cells and organisms, contrasting with detrimental effects induced at high doses. Radiation hormesis is defined as biopositive health effects, such as augmentation of growth and survival, enhancement of immune response, suppression of mutagenesis, and increase in resistance to damages induced by subsequent high dose exposure. Accumulating data on molecular, cellular, and organism levels demonstrate a variety of hormetic phenomena produced by low dose radiation. Living organisms have been exposed to low doses radiation since the early period of evolution, therefore, radiation hormesis may be established at least in part as a defense mechanism, and thus has important implications for health and diseases. In this review, data of radiation hormesis were presented with special emphasis on the responses of organisms. Recent studies also show potential application of low dose radiation for intervention of diseases. Research on radiation hormesis will indisputably contribute to elucidate aging processes

Radiation Hormesis: Stimulatory Effects of Low Doses Ionizing Radiation

High doses of ionizing radiation (HDR) induce a variety of harmfuleffects. However, low-doses radiation (LDR) can conditionally result instimulatory effects in various cells and organisms. Radiation hormesis isdefined as biopositive effects, such as augmentation of growth and survival,enhancement of immune response, suppression of mutagenesis and increase inresistance to the effects of further HDR. Adaptive response refers toLDR-induced resistance to the subsequent HDR. Radioadaptive responsemanifests a wide cross-resistance against oxidative damage from otherstresses. In this presentation, first we would like to introduce briefly thedose effect relationship of ionizing radiation and then review theexperimental, epidemiological and clinical data of radiation hormesis, withspecial emphasis on the studies conducted with whole-body irradiation.Second, we present our data clearly demonstrating radiation hormesis in thewhole body irradiated animals. Living organisms have always lived in thepresence of LDR. Radiation hormesis may be established at least in partevolutionarily as a cellular defense mechanism and thus have importantbiological significance and implications for health and disease. Researchon radiation hormesis will indisputably contribute to elucidate agingprocess.第7回アジア・オセアニア国際老年学会

Induction of radical scavenging ability and suppression of lipid peroxidation in rat liver microsomes following whole-body, low-dose X-irradiation

The aim was to investigate changes in radical scavenging ability and lipid peroxidation in liver microsomal membranes and cooperative of lipid peroxidation by microsomal and cytosolic radical scavengers, 24h after whole-body, low-dose X-irradiation of rats. Male Wistar rats were irradiated with 1-50 cGy of X-rays. Liver microsomal radical scavenging ability was determined using the trapping ability of DPPH, a stable free radical. Microsomal alpha-tocopherol (VitE) content was determined using an electrochemical detector. Microsomal glutathione peroxidase (GPX) activity was determined as the consuming rate of NADPH. Microsomal lipid peroxidation was determined by the thiobarbituric acid method. Low molecular weight radical scavenging ability, including alpha-tocopherol, in rat liver microsomes increased 24 h after whole-body, low-dose X-irradiation, showing a maximum level at 5-10 cGy. Microsomal GPX activity also increased 24 h after 5 cGy irradiation. The lipid peroxidation level in microsomes decreased, showing a maximal suppression at 5 cGy. High-dose irradiation-induced microsomal lipid peroxidation was strongly suppressed cooperatively by microsomal and cytosolic antioxidants induced by low-dose irradiation. Low doses of radiation induce increases in liver microsomal antioxidants, which in turn result in enhancing suppressive ability against microsomal lipid peroxidation cooperatively with cytosolic antioxidants induced by low-dose irradiation

Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors,

Reactive oxygen species play a critical role in the onset of apoptosis induced by various extracellular stimuli, including ionizing radiation. Therefore active regulation of reactive oxygen species-metabolizing enzymes may be one response to an apoptotic stimulus. In this regard, HP100 cells, H(2)O(2)-resistant variants derived from human leukemia HL60 cells, display an interesting phenotype in which the activity of catalase is constitutively high, whereas its mRNA is reduced after X-ray irradiation. In the present study, we investigated the molecular mechanisms underlying this phenomenon. By combining analyses from nuclear run-on, reporter gene transient transfection, genomic footprinting, site-directed mutagenesis, electrophoretic mobility shift analysis, and Western blotting experiments, we found that constitutively elevated catalase expression is strongly regulated at the transcriptional level by both Sp1 and CCAAT-recognizing factors and that much higher levels of nuclear Sp1 and NF-Y are present in HP100 nuclei as compared with HL60 nuclei. In addition, we demonstrated an X-ray-inducible association of a WT1/Egr-related factor with an overlapping Sp1/Egr-1 recognition sequence located within the core promoter of the catalase gene. This association may lead to inactivation of the promoter by disturbing or competing with the transactivating ability of Sp1