The effect of accelerated argon ions on the retina

It has been postulated that high energy heavy ions cause a unique form of damage in living tissue, which results from the high linear energy transfer of accelerated single particles. We have searched for these single-particle effects, so-called "microlesions," in composite electron micrographs of retinas of rats which had been irradiated with a dose of 1 Gy of 570 MeV/amu argon ions. The calculated rate of energy deposition of the radiation in the retina was about 100 keV/micron and the influence was four particles per 100 micron 2. Different areas of the irradiated retinas which combined would have been expected to be traversed by approximately 2400 particles were examined. We were unable to detect ultrastructural changes in the irradiated retinas distinct from those of controls. The spatial cellular densities of pigment epithelial and photoreceptor cells remained within the normal range when examined at 24 h and at 6 months after irradiation. These findings suggest that the retina is relatively resistant to heavy-ion irradiation and that under the experimental conditions the passage of high energy argon ions does not cause retinal microlesions that can be detected by ultrastructural analysis.     

Effect of iron ions on the antioxidant enzyme activities in yeast Saccharomyces cerevisiae

A complex of physiological and biochemical indices has been compared in wild and isogenic catalase-deficient strains of Saccharomyces cerevisiae grown on the media with different iron ion concentrations is 2 times higher in cytosolic catalase deficient yeast. Superoxide dismutase activity grown in the medium with 500 microM of ferrous sulphate. Under such conditions, peroxisomal catalase deficient yeast had a 2-fold decreased activity of superoxide dismutase. There is a significant difference between TBA-reactive substances content of the wild and cytosolic catalase deficient strain. It has been suggested that the repletion of iron ions in the growth medium leads to the formation of lipid oxidation products. Catalase prevents TBA-reactive substances formation in the given conditions and plays a protective role.     

Effect of the magnetic field on the energy of deuterium ions accelerated in the collision of magnetosonic shock waves

A study is made of the effect of the initial magnetic field magnitude on the energy of deuterium ions accelerated in the collision of two magnetosonic shock waves propagating in a deuterium plasma quasi-perpendicularly to the magnetic field. Experiments were carried out at a constant plasma density of ?2.5×10¹³ cm^?3. It is found that, as the external magnetic field decreases from 1.4 to 0.7 T and, accordingly, the magnetic Mach number increases from 1.02 to 2.3, the energy of accelerated ions increases from 3.2 to 7.5 MeV. The maximum number of accelerated ions attains 10⁵–10⁶ particles per shot.     

Influence of metal ions on the biosynthesis of N-acetylglucosaminyl polyprenols by the retina

The following enzymatic process was investigated, catalyzed by an enzyme preparation from the retina of the embryonic chick: UDP-GlcNAc + dolichol phosphate GDPmannose leads to metal ions GlcNAc-P-P-polyprenol + (GlcNAc)2-P-P-polyprenol + Man-(GlcNAc)2-P-P-polyprenol. These reactions were carried out in the presence of a dolichol phosphate mannose-synthesizing system, shown previously to be an activator of GlcNAc-lipid synthesis. The process was also strongly influenced by the choice of the divalent cation used during the reactions. In the presence of Mg2+, not only was the extent of incorporation of radioactivity from UDP-[3H]GlcNAc increased 4-fold into the GlcNAc lipids, as compared to Mn2+, but the relative distribution of the products was affected as well. In the presence of Mg2+ the reaction was driven mainly in the direction of the formation of the first intermediate of the dolichol pathway, GlcNAc-P-P-polyprenol. Many of the other characteristics of the GlcNAc-transferases, such as pH optimum, requirement for dolichol phosphate and specificity for stimulation by sugar nucleotides, were similar for either the Mn2+ or Mg2+ systems. Retinol phosphate could not replace the requirement for dolichol phosphate. The influence of metal ions, in addition to the stimulation by dolichol phosphate mannose, on GlcNAc-lipid synthesis may be aspects of metabolic regulation of the dolichol pathway.     

The mutagenic effect of accelerated heavy ions on E. coli cells

In studying E. coli mutation rate as a function of dose of different types of ionizing radiation it was found that mutagenic efficiency of helium ions (LET-22, 54 and 72 keV/microns) was higher than that of gamma-rays. As LET increased the mutagenic efficiency decreased. The mutation rate for all types of radiation under study was both a power function and a linear-quadratic function of dose.     

Cytogenetic effects induced by accelerated carbon ions with shielding

Our work aims to understand the effects of shielding on the induction of biological damage by heavy charged particles and to compare the shielding effects of different materials at the same LET from two aspects: the biological effectiveness including or not including secondary particles emitted at large angles and the biological effectiveness at different angles with respect to the beam direction. We designed and conducted biological experiments to determine the biological effectiveness of 200 MeV/u carbon ions after traversing different shielding materials (Lucite and aluminium). Whole blood samples, which were either attached to the shielding material (48 mm Lucite or 29 mm aluminium)or positioned at 300 cm away from it at different angles with respect to the beam axis, were exposed to carbon ion beams. For comparison, whole blood samples were exposed directly to 200 MeV/u carbon ions. Chromosomal aberrations in lymphocytes were scored. The results indicated that the biological effectiveness per unit dose was not significantly changed by 48 mm Lucite or 29 mm aluminium, and no significant differences were observed in lymphocytes attached to the target and in lymphocytes positioned at a distance of 300 cm away from the target, at 0o angle of the beam axis. However, when plotted as a function of the number of ions hitting the shielding target, the curves are separated and the shield increases the effectiveness per unit ion. The frequency of chromosomal aberrations at tilted angles behind 29 mm Al and 48 mm Lucite was almost the same. These lesions were considered to be caused by secondary particles due to the passage of particles through the shielding materials.     

Intracellular iron ions regulate the genetic activity of NO-donating agents

This work is a part of a directional search for new crystal donors of nitric oxide (NO), which are promising for complex chemotherapy. The relationships between the physico-chemical properties of NO donors, their genotoxic and mutagenic activities, and the dependence on intracellular iron were studied. New crystal NO donors (di-and trinitrosyl iron complexes with synthetic ligands) were examined for the first time and compared with known NO donors containing natural ligands. All but one compound induced expression of the Escherichia coli sfiA gene belonging to the SOS regulon and exerted a mutagenic effect on Salmonella typhimurium TA1535. These effects were fully or significantly inhibited by the iron(II)-chelating agent o-phenanthrolin, depending on the mono-or binuclear structure of the ligands. The rate of donating free NO in solution did not positively correlate with the genotoxic activity of the crystal NO donors. The genetic activity of all NO donors proved to depend on intracellular iron.     

Induction of apoptosis of splenic lymphocytes in mice by accelerated carbon ions

To assess the capacity of heavy ions to induce apoptosis in lymphocytes, mice have been irradiated with accelerated carbon ions (95 MeV/nucleon) at doses ranging from 0.1 to 4 Gy. Their spleens were removed 24 h later and gently dissociated to prepare a single cell suspension. Mononuclear cells were then maintained in culture at 37 degrees C, and the occurrence of apoptosis in these cells was analysed 24 h later. Lymphocytes were also irradiated in vitro, in the presence of Ac-DEVD-CHO, a potent caspase-3 and -7 inhibitor. Results from three experiments performed at the Grand Accelerateur National d'Ions Lourds (GANIL, Caen, France) are reported here. They indicate that carbon ions induce a marked, dose-dependent, reduction of the spleen weight and cellularity. However, in sharp contrast with spleen cells prepared from X-ray irradiated mice, only a slight increase of apoptosis is evidenced in cultured lymphocytes from mice irradiated with heavy ions. The significance of such results is discussed. So far, few data exist concerning the biological effects of heavy ions, in particular their capacity to induce apoptosis in lymphocytes; the present study provides useful clues for further investigations.     

The effect of picolinic acid and iron ions on the proliferation of SPEV cells

The effect of picolinic acid (PA) on SPEV cell proliferation is found to be different from that on normal and virus transformed NRC cells, and on spontaneously transformed CHO cells. It is shown that SPEV cells are arrested by PA at the end of G1-phase and at the beginning of S-phase and probably in G2-phase of the cell cycle. Ferrous ions remove the G1/S block induced by PA to permit the cell transfer through S-phase. On the one hand, PA chelates ferrous ions from the cells, and on the other one it inhibits the replicative DNA synthesis. It can be suggested that PA may arrest the SPEV cell growth affecting the iron-depend stable radical formation which is introduced into the active centre of ribonucleotiDE reduCTase. This results in the lower enzyme activity.