Biophysik

Interleukin-2 (IL-2) is a cytokine responsible for a variety of immune and non-immune stimulatory and regulatory functions, including the activation and stimulation of cytotoxic cells able to recognize and kill human tumour cells and T-cell proliferation and differentiation. We show that low doses of radiation, in the range commonly received by atomic radiation workers or as a result of minor medical diagnostic procedures (0.25 to 10 mGy), stimulate the expression of IL-2 receptors (IL-2R) on the surface of peripheral blood lymphocytes (PBL) taken from normal human donors. This stimulated surface expression after in vitro irradiation is an indirect effect, resulting from the secretion into the medium of a soluble factor from the irradiated cells. This factor can also stimulate IL-2R surface expression in unirradiated cells. Consequently, radiation stimulation of IL-2R expression in a large population of PBL shows a triggered-type response rather than being proportional to dose. These results demonstrate that normal human cells can respond to doses of radiation in the range of common occupational or medical exposures. The data also demonstrate a possible defence mechanism against environmental stress by which a radiation-exposed cell can use an indirect signalling mechanism to communicate with and influence the biological processes in an unexposed cell.

Survivin is a member of the inhibitors of apoptosis (IAP) protein family that interferes with post-mitochondrial events including activation of caspases. To examine the regulation of survivin expression in response to irradiation with different linear energy transfer (LET), human hepatoma HepG2 cells were irradiated in vitro with X-rays and carbon ions. Cellular sensitivities to low- and high-LET radiation were determined by colony formation. Survivin expression at mRNA and protein level were measured with RT-PCR and Western blot analyses, respectively. Radiation-induced cell cycle arrest and apoptosis were investigated with flow cytometry. We found that low-LET X-rays induced dose-dependent increases in survivin expression. After exposure to high-LET carbon ions, survivin expression gradually increased from 0 to 4 Gy, and then declined at 6 Gy. More pronounced survivin expression, stronger G2/M phase arrest was observed after exposure to carbon ions in comparison with X-rays at doses from 0 to 4 Gy. These observations indicate that there is a differential survivin expression in response to different LET radiations and the cycle arrest mechanism may be associated with it. In addition, our data on induction of apoptosis are compatible with the assumption that survivin expression induced by low-LET X-rays radiation may play a critical role in inhibiting apoptosis. However, after irradiation with ions, an anti-apoptotic function of survivin is not evident, possibly because of the serious damage produced by densely ionizing radiation.

The rate of cell entry from the compartment of hematopoietic early progenitor cells into differentiation was determined in sublethally irradiated mice. By use of the criterion of repopulating ability, transplantation of 5-(125I) iodo-2′-deoxyuridine labeled bone marrow cells into fatally irradiated syngeneic recipients allows to measure the relative number of early progenitor cells lodging in the spleen and the turnover of these cells in the donors. Following 450 rad the relative number of transplantable early progenitor cells in S-phase recovers to normal within 2 weeks and stabilizes after 5 weeks. At this time, the labeled progenitors turn over with a half-time of 1.4–2.2 days; the respective times for unirradiated mice are 1.5–1.8 days. Thus, quantitative and qualitative residual radiation damage that is known to exist in the compartment of CFU-S, is disguised within 2–5 weeks after irradiation by proliferative compensation in the entirety of early hemopoietic precursor cells which are here defined by their capacity of selfrenewal and delivery of differentiated cells and of seeding to spleens of lethally irradiated recipients.

The risk of cancer after diagnostic X-rays received as fetus or during early childhood has been investigated in many studies. The results of recent epidemiological studies are summarized in a present systematic review. The strategies for literature search, inclusion criteria, and items for study quality assessment were defined in the study protocol. All epidemiological case control and cohort studies published in English between 1990 and 2006 that reported at least the size of the study population and risk estimates were included. Results were summarized separately for pre- and postnatal exposure and for each cancer site. Nineteen case control studies and six cohort studies matched the inclusion criteria. No association of leukemia with prenatal exposures was observed in nine case control studies. Heterogeneous results were found for postnatal exposures and leukemia in four studies. No significant effect of pre- and postnatal X-ray exposure was observed for other cancer sites (non-Hodgkin lymphomas, solid tumors and brain tumors). Most studies have limitations in study design, study size, or exposure measurement, and involve very low exposures. These results thus do not contradict previous evidence accumulated since 1956 indicating risk increases associated with prenatal X-ray exposure. Computed tomography is not covered in the studies and needs to be investigated in the future.

Sowohl nach UV-Bestrahlung (254 nm) als auch nach Röntgenbestrahlung bei 20 °C ergeben sich für Pyridoxin und einige schwefelhaltige Pyridoxinderivate gleiche Radikalzustände. Wahrscheinlich befindet sich ein unpaares Elektron in der Methylgruppe der Stellung 4 oder 5. Bei den Derivaten, die den Schwefel in Form des Sulfhydryls enthalten, findet eine Radikalwanderung zum Schwefel statt. Dabei wird der Radikalzustand am Schwefel des 4-Mercaptopyridoxins schneller gebildet als im Falle des 5-Mercaptopyridoxins. Die Disulfidbindung des Pyrithioxins ist gegenüber den Sulfhydrylbindungen der Mercaptopyridoxine stabiler. Ist der Schwefel in Form eines Thioäthers vorhanden (4,5-Methylensulfidpvridoxin), so erhält man ein Radikal vom Alkyltyp, ohne daß anschließend eine Radikalwanderung zum Schwefel auftritt. Die ESR-Untersuchungen zeigen darüber hinaus, daß die Bildung und das Zeitverhalten der Radikale nicht nur von ihrer unmittelbaren Umgebung, sondern auch von der ganzen Struktur des Moleküls abhängig sind.

Despite the rareness of radiation accidents, their potential consequences can be very serious, and appropriate medical management requires sufficient preparatory planning. To identify necessary factors for sufficient preparatory planning, three different radiation accidents were analyzed, i.e. the accidents in Goiânia, Brazil, 1987; Lilo, Georgia, 1997; and Tokai-mura, Japan, 1999. These radiation accidents have been chosen specifically because they provide a wide spectrum of potential radiation accident scenarios. After a brief description of the accidents and the following medical management, the measures taken are analyzed in terms of diagnosing radiation-induced health damage, determining the cause, dealing with contamination/incorporation, pathophysiological and therapeutic principles, preparatory planning, national and international cooperation and training. Several important factors are identified that should be considered in preparatory planning, i.e. preventing delayed diagnosis and training of medical personnel. Due to limited national resources, an intensified international cooperation to manage medical radiation accidents is of great importance.

The various aspects of formation and repair of radiation-induced double-strand breaks (DSB) are summarized. Concerning the structure of DSB found in irradiated cells, enzymatic and microdosimetric analysis hints at complex damage of the DNA structure at the position of a DSB. With increasing LET, the DSB damage may be more complex than that induced by low-LET irradiation. Most of the DSB are repaired in the irradiated cell; apparently the kinetics of DSB repair and the fraction of unrejoined DSB determine cell survival or cell death. We do not know the details of the complex machinery of DSB repair; certaintly recombination processes are involved, but there are still contradictions between our current knowledge about the mechanisms of recombinational DSB repair and the observed kinetics.