The psychological effects of ionizing radiation

This paper presents a case study of eleven men who were exposed to non-background ionizing radiation as active participants in the United States' atmospheric nuclear tests. Each of the subjects has developed a virtually identical complex of debilitating psychiatric symptoms. The content of these symptoms is almost entirely focused upon the health effects of the radiation to which each of the subjects was exposed. This symptom complex appears to comprise a syndrome. The symptom structure and course of this syndrome suggests three hypotheses: The syndrome appears to be a pathological development of the self diagnostic belief (that one has been physically harmed by radiation) into a set of symptoms that elaborate upon and express this belief. The self diagnostic belief develops as a means of resolving any one of the various medical mysteries that an individual can experience subsequent to exposure to radiation. Development of the syndrome is a consequence of exposure to non-background ionizing radiation. The paper discusses the evidence for these hypotheses and suggests future research directions.     

Dose rate effects of low-LET ionizing radiation on fish cells

Radiobiological responses of a highly clonogenic fish cell line, eelB, to low-LET ionizing radiation and effects of dose rates were studied. In acute exposure to 0.1–12 Gy of gamma rays, eelB’s cell survival curve displayed a linear–quadratic (LQ) relationship. In the LQ model, α, β, and α/β ratio were 0.0024, 0.037, and 0.065, respectively; for the first time that these values were reported for fish cells. In the multi-target model, n, D _o, and D _q values were determined to be 4.42, 2.16, and 3.21 Gy, respectively, and were the smallest among fish cell lines being examined to date. The mitochondrial potential response to gamma radiation in eelB cells was at least biphasic: mitochondria hyperpolarized 2 h and then depolarized 5 h post-irradiation. Upon receiving gamma rays with a total dose of 5 Gy, dose rates (ranging between 83 and 1366 mGy/min) had different effects on the clonogenic survival but not the mitochondrial potential. The clonogenic survival was significantly higher at the lowest dose rate of 83 mGy/min than at the other higher dose rates. Upon continuous irradiation with beta particles from tritium at 0.5, 5, 50, and 500 mGy/day for 7 days, mitochondria significantly depolarized at the three higher dose rates. Clearly, dose rates had differential effects on the clonogenic survival of and mitochondrial membrane potential in fish cells.     

Low-dose ionizing radiation effects on differentiation of HL-60 cells

The biological effects of low-dose radiation have attracted attention, but data are currently insufficient to fully understand the beneficial role of the phenomenon. In the present study, we have investigated the effects of low doses of gamma-irradiation alone and in combination with all-trans-retinoic acid (RA) on proliferation, apoptosis and differentiation of the human promyelocytic leukemia HL-60 cells. Changes in cell behavior and protein expression were determined with the use of light and fluorescent microscopy, immunocytochemical and Western blot analysis. Low-dose irradiation with 1–100 cGy caused a dose-dependent inhibition of HL-60 cell proliferation, and induced apoptosis and differentiation to granulocytes with an increase in the number of CD15-positive cells. Pre-irradiation with 1–100 cGy for 24 h before treatment with RA promoted apoptosis but did not impair RA-induced differentiation. Both processes were associated with a decrease in the expression of the proliferating cell nuclear antigen (PCNA), BCL-2, c-MYC, and changes in both cytosolic and nuclear levels of protein tyrosine-phosphorylation as well as protein kinase C alpha or beta isoforms. These results demonstrate the beneficial role of low-dose irradiation in modulating leukemia cell proliferation, differentiation and apoptosis.     

A stochastic model of the effects of ionizing radiation on mammalian cellsin vitro

A new, more realistic model of the action of ionizing radiation on mammalian cells growingin vitro is presented. Although this model requires a large number of parameters, these are linked to biologically observable quantities rather than being abstract sensitivities, as had previously been the case. Three different stochastic processes are required: {X(t);t ∈ [0, τ]}, representing damage alterations during irradiation; {(X(t), S(t));t ∈ [τ, τ+T _D]}, representing changes in both damageX(t) and cell cycle positionS(t) during the post-irradiation cell cycle; and {N _x(t);t ∈ [0,T _G]}, representing the subsequent colony growth process conditioned on the value ofX(τ+T _D). The assumptions used to define these processes extend a previous model of short term DNA damage formation and repair (Nelson S. J. 1982,Radiat. Res. 92, 120–145) to include the influence of cell cycle progression on damage in the irradiated cell and the effect of permanent inherited damage on the daughter cells' colony growth pattern. Expressions corresponding to commonly measured radiation effects are derived from the model and compared with predictions from previous models. It is found that these previous models oversimplified the mechanism of radiation action because they did not adequately represent repair during irradiation, the influence of radiation-induced cycle delays and damage inheritance by any daughter cells. Suggestions are then made for ways in which the new model can be used to test the importance of these effects.     

Cell-density dependent effects of low-dose ionizing radiation on E. coli cells

The changes in genome conformational state (GCS) induced by low-dose ionizing radiation in E. coli cells were measured by the method of anomalous viscosity time dependence (AVTD) in cellular lysates. Effects of X-rays at doses 0.1 cGy--1 Gy depended on post-irradiation time. Significant relaxation of DNA loops followed by a decrease in AVTD. The time of maximum relaxation was between 5-80 min depending on the dose of irradiation. U-shaped dose response was observed with increase of AVTD in the range of 0.1-4 Gy and decrease in AVTD at higher doses. No such increase in AVTD was seen upon irradiation of cells at the beginning of cell lysis while the AVTD decrease was the same. Significant differences in the effects of X-rays and gamma-rays at the same doses were observed suggesting a strong dependence of low-dose effects on LET. Effects of 0.01 cGy gamma-rays were studied at different cell densities during irradiation. We show that the radiation-induced changes in GCS lasted longer at higher cell density as compared to lower cell density. Only small amount of cells were hit at this dose and the data suggest cell-to-cell communication in response to low-dose ionizing radiation. This prolonged effect was also observed when cells were irradiated at high cell density and diluted to low cell density immediately after irradiation. These data suggest that cell-to-cell communication occur during irradiation or within 3 min post-irradiation. The cell-density dependent response to low-dose ionizing radiation was compared with previously reported data on exposure of E. coli cells to electromagnetic fields of extremely low frequency and extremely high frequency (millimeter waves). The body of our data show that cells can communicate in response to electromagnetic fields and ionizing radiation, presumably by reemission of secondary photons in infrared-submillimeter frequency range.     

The acute effects of ionizing radiation on DNA synthesis and the development of antibody-producing cells

Ionizing radiation inhibited the development of specific haemolysin-producing cells (PFC) and depressed the incorporation of (3H) thymidine by rabbit spleen explants responding to SRC in the culture medium. In contrast to these effects, the rates of incorporation of precursors for protein and RNA synthesis were much less affected. The depression of (3H) thymidine incorporation was found to result from a quantitative reduction of new DNA synthesis, without any change in the proportion of labelled cells, at any time after irradiation. The DNA synthesis occurring in these cells preparing to develop antibody-producing capacity was thus radio-sensitive, but the exact nature of the defect resulting from exposure to radiation requires further study.     

The effect of ionizing radiation on lipid metabolism in lymphoid cells

Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose.     

The effects of ionizing radiation on cell cycle progression in ataxia telangiectasia

Although ataxia telangiectasia (AT) cells are more sensitive than normal cells to killing by ionizing radiation, their DNA synthesis is more resistant to inhibition by radiation. It was thought that this anomaly in DNA synthesis was likely to perturb cell cycle progression. Flow cytometry and the fraction of labelled mitoses (FLM) were used to investigate effects of irradiation in normal and AT cell lines. The FLM indicated that radiation apparently induced a longer G2 delay in normal cells than in AT cells. However, flow cytometry showed that radiation induced much larger and more prolonged increases in the proportion of G2 cells in AT than in normals. AT populations also showed much larger postirradiation decreases in viable cell numbers. These data suggest that a large proportion of the radiosensitive AT cells are not reversibly blocked in G2 but die there, and never proceed through mitosis. The less radiosensitive normal cells are delayed in G2 and then proceed through mitosis. We suggest that the apparently shorter radiation-induced mitotic delay seen in AT cells by FLM is not real but is an artifact arising from perturbation of steady state conditions by selective elimination of a particular cohort of AT cells. Accumulation of AT cells in G2 is compatible with radiosensitivity of these cells and may arise from a defect in DNA repair or an anomaly in DNA replication.     

Differential effects of adiponectin in osteoblast-like cells

Abstract

The skeleton should maintain an adequate volume, vigour and strength to carry out the role for which it is designed: to hold the whole soft tissue mass that shapes the body and to protect the vital organs. To fulfil this task a satisfactory food intake is required and regulators that are released in the feeding and fasting states, among other signals indicate how much soft mass needs to be built up. Those signals include the secretion of adipocytokines which could represent a relevant link between soft mass (adipose tissue) and skeleton. We studied the presence of adiponectin receptors (AdipoR1, AdipoR2) and its direct effects in osteosarcoma cell line Saos-2. The results indicated that adiponectin receptors were present in the osteoblastic cells with a higher expression of AdipoR1. Human recombinant globular adiponectin was able to increase viability levels and decrease cytotoxicity rates in cell cultures. Also, adiponectin significantly inhibited alkaline phosphatase activity in supernatants. Osteoprotegerin mRNA expression was significantly reduced after 72?h treatment. The FOS induction was studied and the results exhibited a significant increase caused by adiponectin. In conclusion, all these observations suggest that adiponectin influences bone metabolism decreasing the levels of bone formation. Regulators of adiponectin or its receptors could be circulating to modulate the activities of this peptide.