The growth arrest and DNA damage-inducible protein 45alpha (GADD45a) gene is responsive to a variety of DNA-damaging agents. It is known that induction of the GADD45a gene is regulated in a p53-dependent manner after ionizing irradiation. Our previous study showed that X-ray irradiation increased the transcription rate of the GADD45a gene much earlier than the maximum accumulation of stabilized p53 protein in human myeloblastic leukemia ML-1 cells. We hypothesized that some transcription factor(s) may cooperate with p53 in regulating the GADD45a gene early after the irradiation of ML-1 cells. This idea is supported by recent studies showing that the p53-dependent activation of several genes in human and mouse cells requires some additional transcription factors, such as Sp1, GKLF, Ets1, and IRF-1. To examine the possible involvement of cooperating factors in transcriptional regulation of the GADD45a gene by ionizing radiation, we comprehensively searched for the X-ray-inducible binding locus of the nuclear factor throughout the upstream region (-2244 bp/+89 bp) and the third intron (+1389 bp/+2488 bp) of the GADD45a gene by EMSA using 136 probes. The X-ray-responsive binding of nuclear factors was detected at eight loci. Oct, NF-κB, HNF, NF-AT, and KLF family transcription factors were identified by a competition assay. It is possible that some of these factors cooperate with p53 to mediate transcriptional regulation of the GADD45a gene after ionizing irradiation.

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Monthly atmospheric depositions of ⁹⁰Sr and ¹³⁷Cs have been observed at the Meteorological Research Institute (MRI), Tsukuba, Japan. This study reports temporal trends and levels of ⁹⁰Sr and ¹³⁷Cs depositions in the 1990s. Although the current ⁹⁰Sr and ¹³⁷Cs concentrations declined dramatically, they have been found continuously in the deposition samples throughout the 1990s. During this period, the annual ⁹⁰Sr (¹³⁷Cs) deposits at MRI ranged from 70-180 (140-350) mBq/m²/year. With a sufficiently long time series, the decreasing trend of the deposition evidently differs from the past stratospheric fallout; it is far slower. Thus, reservoirs other than the stratosphere provide small amounts of ⁹⁰Sr and ¹³⁷Cs to the atmosphere. A simple calculation clearly refutes the significance of the ocean as a potential source of airborne anthropogenic radioactivity. We will demonstrate that these radionuclides in the deposited materials originate from resuspension processes (soil dust suspension processes). The temporal trends of the time series monitoring reveal differences from those in the UNSCEAR Report 2000, which were predicted by a model that disregarded resuspension. The specific activity of ⁹⁰Sr (¹³⁷Cs) in the annual depositions exhibited a 10-year (20-year) half-life. Those data were comparable with values reported in the literature for the half-residence time (HRT) of ⁹⁰Sr and ¹³⁷Cs in Japanese surface soils. They were also comparable to those calculated from nationwide data of ⁹⁰Sr and ¹³⁷Cs concentrations in the surface soil (0-10 cm) obtained from the Ministry of Education, Culture, Sports, Science and Technology Environmental Radiation Database (the MEXT Database). Regarding the activity ratio of ¹³⁷Cs/⁹⁰Sr, the Japanese nationwide surface soil data collected during the 1990s in the MEXT Database (median: 5.3, n = 584) did not accord with that in the deposition samples (average: 2.1, n = 82) at MRI. This supports our previous hypothesis that Asian dust may transport a large fraction of anthropogenic radioactivity into the Japanese atmosphere. We need to study the fate of long-lived anthropogenic radioactivity dispersed in the environment over greater spatial and temporal scales.

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The radiosensitizing effect of a phosphoinositide-3 kinase (PI3K) inhibitor, wortmannin, has been studied rather extensively, but there have been few studies on the radiosensitizing effect of another PI3K inhibitor, LY294002. In this report, we present the radiosensitizing effect of LY294002 using normal human cells. Clonogenic cell survival indicated that LY294002 enhanced the killing effect of γ-rays in a dose-dependent manner, although this drug by itself did not affect the cell killing. To obtain a 10% cell survival, about one half of the radiation dose was needed when cells were treated with 50 μM LY294002 as compared to cells without the drug. A mild inhibition of repair of DNA double strand breaks (DSBs) was observed in irradiated normal human cells pre-treated with LY294002 (50 μM). At the interphase chromosome level, we also observed an increase in the number of residual breaks when irradiated cells were pre-treated with this drug (about 2-fold at 5 Gy). These results suggest that the inhibition of DSB repair mediated the radiosensitizing effect of LY294002 at the dose level that we used.

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The pulse radiolysis technique has been employed to determine the initiation and propagation rates of different transient species involved in the polymerization of N-isopropylacrylamide (NIPA) in aqueous solutions. Polymerization by anionic mechanism has been observed to be faster than by the free-radical mechanism. The kinetic, spectroscopic and redox properties of the transient species formed upon reaction of primary radiolytic species of water radiolysis with NIPA have been evaluated. The one-electron oxidation potential for the formation of a radical cation is quite high (>2 V), but the one-electron reduction potential is low (in the range of -0.3 to -0.7 V). The radical anion of NIPA is able to undergo an electron-transfer reaction with MV²⁺, and has a pK_a value of 3.2. The tert-butyl alcohol radical was also able to initiate polymerization. Gamma radiation-induced polymerization studies showed that the reaction of H^·/^·OH/e_aq^-/tert-butyl alcohol radicals with NIPA results in a nearly equal yield of the gel fraction. The hydrogel is observed to have very little swelling below pH 3 and above pH 10. The linear polymer of NIPA formed by irradiating dilute aqueous solution is found to be a thermosensitive polymer with lower a critical solution temperature (LCST) of ~33°C. The diameters of polymer molecules were 290 and 20 nm at temperature below and above LCST, respectively.

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Aim: The pathogenesis of delayed encephalopathy induced by heavy-ion irradiation was investigated experimentally in cats. The left cerebral hemispheres were irradiated with 15-40 Gy of heavy ions (carbon), and histologically and morphometrically examined 12 months later. Results: In the irradiated cerebral white matter the following occurred as the dose increased: astrocytic swelling, then the dilatation of small blood vessels with a fibrous thickening of the wall, and then loosening of the white matter with cavity formation and diffuse albumin deposition. Pathological features of these cavities suggested that they are induced by long-standing edema. Although the dilated vessels were arteries, veins, and capillaries, arteriovenous shunt and damage of the smooth muscle cells of the arterial media were absent. Changes of the cerebral cortex were scarce. Morphometrically, the irradiated cerebral white matter was swollen, and the capillary density tended to be reduced in the deep cortex and subcortical white matter, but this effect was not dose dependent. Conclusion: Heavy-ion irradiation induces delayed encephalopathy in cats, preferentially involving the white matter. The cardinal pathogenesis was long-standing edema of the white matter due to vascular hyperpermeability, and the vascular dilatation seemed to be caused by a reduction in the vascular bed and/or hemoconcentration due to hyperpermeability.

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The mouse lymphoma cell line LX830 is an X-ray-hypersensitive mutant. Complementation tests between LX830 cells and radiation-sensitive mutants of M10 (Xrcc4 deficient cells) or SX10 (DNA ligase IV deficient cells) cells showed that M10 cells did not complement LX830 cells, but SX10 cells did, suggesting that LX830 cells would belong to the X-ray-cross complementation group (XRCC4). A sequence analysis of Xrcc4 cDNA in LX830 cells disclosed a transition of G to A at nucleotide position 129, which resulted in a change of tryptophan (43) to a termination codon. Transfection of the mouse Xrcc4 cDNA rescued the X-ray sensitivity of the mutant cells. LX830 is an Xrcc4-deficient cell line bearing a termination codon in exon 2 of the Xrcc4 gene and no wild-type Xrcc4 gene.

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Sanazole (AK-2123) (N-2′-methoxy ethyl)-2-(3″-nitro-1″-triazolyl)acetamide, which has completed phase III clinical trials as a radiosensitizer, enhanced γ-radiation induced apoptosis in murine fibrosarcoma upon i.p. administration at 40 mg/kg body weight one hour prior to irradiation. A microscopic examination of Giemsa-May-Grunwald stained cells has shown a higher frequency of condensed nuclei and fragmented nuclei in the tumor cells. The administration of sanazole to tumor-bearing animals enhanced the radiation-induced internucleosomal fragmentation in the nuclear genome of tumor cells. Higher levels of caspase-3 activity were also observed in the cell extracts of tumours from AK-2123 administered mice. Exposure to γ-radiation of AK-2123-treated mouse further enhanced the caspase-3 activity, indicating the induction of apoptosis. The radiation sensitization property of sanazole was discernible by comparing the relative tumor diameter following irradiation after i.p. administration of AK-2123 and irradiation alone; it was higher during the first few days followed by the treatment.

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