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

Phosphatidylserine induces apoptosis in CHO cells without mitochondrial dysfunction in a manner dependent on caspases other than caspases-1, -3, -8 and -9.

Treatment of Chinese hamster ovary K1 cells with phosphatidylserine (PS) caused typical　apoptosis with distinct morphological and biochemical features in a dose- and time-dependent manner. However, unlike camptothecin-induced apoptosis, changes in mitochondrial transmembranepotential were not observed. In addition, cytochrome c release did not occur in PS-induced apoptosis. A pan caspase inhibitor, Z-VAD, significantly inhibited the apoptosis, but inhibitors of caspase-1, -3, -8 and -9 did not. Activities of caspase-1, -3, -8 and -9 were increased bytreatment of the cells with camptothecin, but not with PS. These results suggest that PS-induced apoptosis occurs without the collapse of mitochondrial transmembrane potential and without the release of cytochrome c, in a manner independent of caspase-1, -3, -8 and -9

Effects of Pre-exposure on the Survival and Hematological Changes in the Lethally Irradiated C57BL Mice

Exposing mice to 0.5 Gy 2 weeks before lethal (around LD50/30) whole-body irradiation has been reported to induce marked radio-resistance and to rescue them from "bone marrow death." It is widely accepted that cause of the death after dose around LD50/30 is mainly mediated by hematological failure. In order to elucidate the mechanism underlying the adaptive response, we examined effects of 0.5 Gy pre-exposure on the survival and hematological changes in C57BL mice irradiated with 6.5 Gy X-rays. The pre-exposure 2 weeks before the challenging dose enhanced survival to 77% at day 30, whereas without exposure, the survival decreased to 20 % at day 20 and 0% at day 26 after 6.5 Gy. Hematopoietic progenitor CFU-GM in the pre-irradiated mice began to recover around day 20 and then increased markedly. However, peripheral blood cell counts depleted to reach a nadir at day 20, regardless of the pre-irradiation, in spite of marked difference in the survival between the pre-irradiated and non-pre-irradiated mice. These cell counts in the pre-exposed mice recovered at day 30. We found that OK432, a bio-response modifier, could further enhance the survival of pre-exposed mice to 97%, when administrated 2 days before 0.5 Gy. The OK432 administrated mice also survived without recovery of the peripheral blood cell counts at day 20. These results manifest that the lethally irradiated mice are rescued by pre-exposure without recovery of hematological failure at least by day 20. Furthermore, we have observed long-term effect of pre-exposure for 1 year. More than half of the survivor of the pre-irradiated mice and the OK432 injected mice survived 1 year, even though they showed a variety of abnormalities.低線量放射線の生物影響に関する国際シンポジウ

Roles of protein kinase C in radiation-induced apoptosis signaling pathways in murine thymic lymphoma cells (3SBH5 cells)

Murine thymic lymphoma cells and 3SBH5 are quite sensitive to X-rays and undergo apoptosis shortly after X-irradiation. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), blocked the radiation-induced apoptosis in the 3SBH5 cells. On the other hand, chelerythrine, a PKC inhibitor, enhanced the radiation-induced apoptosis. These results suggest that PKC plays a key role in the regulation of radiation-induced apoptosis in 3SBH5 cells. Irradiation alone had no effect on the distribution of PKC subtypes (alpha, betaI, betaII and delta) in the 3SBH5 cells. The amounts of PKC beta I in the cytosol of the 3SBH5 cells decreased in the cells pretreated with PMA. Irradiation did not change the decrease of PKC beta I. In contrast, treatment with PMA had no effect on the distribution of the other PKC subtypes. PMA appears to influence processes of radiation-induced apoptosis through the change in the distribution of PKC beta I. In addition, it was demonstrated that immunoprecipitates by anti-PKC alpha antibody included Raf-1, one of stress response proteins, in 3SBH5 cells after irradiation. These results suggest that PKC alpha might participate as a regulator in radiation-induced apoptsis, but PKC beta I might influence the apoptosis indirectly through the PMA-induced change of the distribution