Within the framework of radiation biophysics research in the hadrontherapy field, split-dose studies have been performed on four human cell lines with different radiation sensitivity (SCC25, HF19, H184B5 F5-1 M10, and SQ20B). Low energy protons of about 8 and 20 keV/μm LET and gamma-rays were used to study the relationship between the recovery ratio and the radiation quality. Each cell line was irradiated with two dose values corresponding to survival levels of about 5% and 1%. The same total dose was also delivered in two equal fractions separated by 1.5, 3, and 4.5 hours. A higher maximum recovery ratio was observed for radiosensitive cell lines as compared to radioresistant cells. The recovery potential after split doses was small for slow protons, compared to low-LET radiation. These data show that radiosensitivity may not be related to a deficient recovery, and suggest a possible involvement of inducible repair mechanisms.

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A synergistic interaction of hyperthermia with ionizing or UV light (254 nm) radiation was analyzed in experiments with yeast cells. For a fixed dose rate of radiation, the synergism was shown to be observed only within a definite temperature range (40-45°C), inside of which there was an optimal temperature to achieve the highest synergism. The effectiveness of the synergistic interaction was smaller for haploid cells than for diploid cells. Experimental data from diploid yeast cells evidenced the significance of the exposure rate in the synergistic interaction of heat combined with ionizing or ultraviolet radiation. The data show that the less is the intensity of radiation, the lower is the temperature that should be used to provide some definite, or highest, synergistic interaction with the radiation. To demonstrate the significance of this rule for other cellular systems, the results of other authors published for bacterial spores and mammalian cells are discussed. Calculations from these results have confirmed the revealed relationship between the dose rate and the exposure temperature. On this basis, it is inferred that synergism may take place at small intensities of harmful environmental factors existing in the biosphere. Hence, any assessment of the health or environmental risks should take into account synergistic interactions between harmful agents.

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The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates with their radiosensitivity. This correlation has been demonstrated in radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is defective in a DNA end-binding protein, Ku80, which is a component of a DNA-dependent protein kinase complex used for joining strand breaks. However, Ku80-deficient cells are known to be retarded in cell proliferation and growth as well as other yet to be identified defects. Using custom-made 600-gene cDNA microarray filters, we found differential gene expressions between the wild-type and XRS-5 cells. Defective Ku80 apparently affects the expression of several repair genes, including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected. In addition, for large numbers of growth-associated genes, such as cyclins and clks, the growth factors and cytokines were also affected. Down-regulated expression was also found in several categories of seemingly unrelated genes, including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress protein, proto-oncogenes and tumor suppressors, transcription and translation factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in Ku80 expression. The diversified groups of genes being affected could mean that Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is also involved in transcription regulation. Our data, taken together, indicate that there are specific genes being modulated in Ku80- deficient cells, and that some of the DNA repair pathways and other biological functions are apparently linked, suggesting that a defect in one gene could have global effects on many other processes.

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Because background radiation in an irradiation room creates a problem with the PG-SPECT (Prompt Gamma-ray Single Photon Emission Computed Tomography) system, which evaluates the absorbed dose for the Boron Neutron Capture Therapy treatment, optimization of a collimator system was performed while taking the shielding of background gamma-rays into consideration. Assuming that a parallel-beam collimator is used, three parameters - the diameter of a hole, the length of the collimator, and the number of detectors (the number of holes of the collimator) - were selected for optimization. Because the combinations of these parameters are limitless, it is difficult to determine them simultaneously. Therefore, a statistically derived Optimization Criterion has been proposed to optimize these parameters. When the spatial resolution was 1 cm-FWHM (full width at half maximum), the optimal diameter of the collimator was 5.4 mm, the optimal length was 321 mm, and the optimal number of detectors was 31 × 31.

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Although thiol-containing compounds have long been known to possess radioprotective properties, their therapeutics utility is limited by their side effects at radioprotective doses. In this study, a series of 2-iminothiazolidine derivatives were prepared and their toxicity and radioprotective effects in NMRI mice were determined using the LD_50/30 end point. The LD₅₀ values, as determined by a Probit analysis, were between 11 and 14 mg/kg. For studying radioprotective effects, one-sixth of the toxic LD₅₀ values were used, namely 2 and 2.2 mg/kg. To evaluate the radioprotective capabilities, mice were exposed to lethal doses of cobalt-60 γ-radiation alone or in the presence of compounds. The percentage survival of mice at 30 days for these compounds compared to control mice were 10 to 30% when injected 15 and 30 minutes before γ-irradiation. They were significant compared to the control group (P<0.05). 2-Imino-3-(benzoylmethyl)thiazolidine derivatives showed different radioprotective effects when injected at different times before irradiation, but were not statistically significant from each other (P>0.05).

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Various types of mutation induced by oxidative DNA damage, induced by hydrogen peroxide and riboflavin photosensitization, were determined in Escherichia coli (E. coli) mutants deficient in endonuclease III (endo III) and endonuclease VIII (endo VIII). The majority of hydrogen peroxide-induced and spontaneous mutations consisted of G:C to A:T and to T:A base changes, shown on the mutation assay system by a reversion at a specific site of the lacZ gene. Base changes were also localized at G:C pairs in the mutation of the supF gene, induced by riboflavin photosensitization, which specifically yields 7,8-dihydro-8-oxoguanine (8-oxoG). G:C to T:A and to C:G transversions dominated in both mutants. These results suggest that endo III and endo VIII are involved in the repair of oxidative lesions of guanine.

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