To evaluate the feasibility of using radiosensitivity of peripheral leukocytes as a predictor of clinical therapeutic responses to radiosurgery in individuals with cerebral arteriovenous malformation (AVM), we enrolled 18 patients years after they had received Gamma Knife radiosurgery for their cerebral AVM. The AVMs were shown with different degrees of regression in size in posttherapeutic periods. The peripheral leukocytes of these patients were collected at the last neuroimaging follow-ups. The leukocytes, before and 1 and 2 h after 8 Gy external gamma-irradiation, were evaluated for the amounts of DNA double-strand breaks (DSB) in 50 randomly selected individual nuclei by the neutral single cell gel electrophoresis, or so-called comet analysis. After being adjusted for gender and age at radiosurgery, the individuals with less posttherapeutic regression in AMV sizes or relatively poor or inadequate responses to radiosurgery were shown to have significantly higher DSB repair capacity on their leukocytes by comet analysis. These results suggested that in vitro radiosensitivity of peripheral leukocytes may provide valuable information for predicting therapeutic response or for adjusting irradiation doses in AVM radiosurgery.

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Human erythrocytes were exposed to γ-rays and α-particles to assess radiation-induced membrane damage and hemoglobin oxidation and denaturation. With all parameters measured, the α-particles proved to be less efficient than the γ-rays. The time-dependence of hemolysis showed also clear differences: with the γ-rays the process was faster, reaching saturation after 40–90 min (depending on dose), but with the α-particles the final level was attained only after about 3–7 h. Hemoglobin oxidation and denaturation could be measured only after γ-exposure, but they were negligible with the α-particles when comparable doses were applied. These results are interpreted by proposing that OH-radicals, whose yields are smaller with densely ionizing radiation, play a crucial role in the induction of the processes for radiation-induced erythrocyte damage.

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Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast CD, yeast CD/UPRT, and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by RT-PCR and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-FC and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p < 0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies.

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Poly(vinylbenzyltrimethylammonium chloride) (PVBT) has been synthesized by radiation-induced polymerization of Vinylbenzyltrimethylammonium chloride (VBT). The viscosity average molecular weight of synthesized polymer was estimated to be ~10⁵ by viscosity measurements. The radiation-induced affects on PVBT have been investigated by steady-state and pulse radiolysis (PR) techniques. The reactions of primary radicals ^·OH, e_aq^-, and H^· generated by the radiolysis of water with PVBT were studied. The reactions of some other species such as N₃^·, Cl₂^·-, Br₂^·-, SO₄^·-, and CO₂^·- with PVBT were also investigated. The results indicate that the reactivity of these species toward PVBT is lower then that with the monomer VBT. The rate constants for the reactions of OH radical and H atom with PVBT were evaluated both by competition kinetics and by direct observation of the buildup of transient species. The difference in the rate constant values evaluated by the two methods indicated that ^·OH and H^· react with PVBT to give more than one species. It was observed that the OH radical and H atom react with PVBT in different manners. Near neutral pH, the OH radicals react to form an adduct and to generate a radical by abstracting methylenic H atom. The H atom, however, also abstracts the H atom from the PVBT backbone. The rate constant value for the reaction of hydrated electron with PVBT was found to be 3.1 ¤ 10⁹ dm³ mol^-1 s^-1. Steady-state irradiation studies of the aqueous PVBT solution indicated that PVBT predominantly undergoes cross-linking on irradiation. Cross-linking is a function of dose rate, concentration, and ambient of irradiation. At concentrations < 2%, only intramolecular cross-linking takes place, whereas beyond this concentration, the intermolecular cross-linking of polymer chains takes place to form a soft gel. The gel dose (D_gel) is a function of the ambient of irradiation.

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We measured and compared the oxygen partial pressure (pO₂) profiles in experimental tumors after irradiation with carbon ions and with X-rays. The NFSa fibrosarcomas grown in the hind legs of C3H male mice received isoeffect single doses of carbon ions or X-rays. Coaxial oxygen microelectrodes of high spatial resolution were inserted into the tumor with 20 μm steps by a computerized micromanipulator. The number of pO₂ peaks that reached 15 mmHg were at least 0.45 per 3,000 μm in unirradiated tumors and significantly increased to 1.55 per 3,000 μm as early as day 1 of carbon-ion irradiation (p < 0.001). The tumors that received X-ray irradiation also significantly increased pO₂ peaks, but as late as day 3. The time course of pO₂ peak appearance in the present study coincides with a previous report where reoxygenation was measured by paired growth delay assay. The pO₂ peaks appeared selectively in peripheral regions of X-ray irradiated tumors, but they appeared rather homogeneously in the tumor after carbon-ion irradiation. It is concluded that carbon-ion irradiation reoxygenated the NFSa fibrosarcomas earlier in time and deeper in space than the X-ray irradiation did.

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Japanese catfish contaminated by ¹³⁷Cs have been used to investigate how dressing and cooking methods affect the removal of radioactivity from the fish. During the dressing, 6.0% of the initial ¹³⁷Cs activity in live fish was removed by washing them, and a further 30.3% of this activity relative to the washed fish was removed by discarding the nonedible body parts (such as the skeleton, fins, visceral mass, liver, and kidney) and by washing the chopped edible remains. Fish curry was cooked with various spices, vegetable oil, and greens and other vegetables following a method commonly used in Southeast Asian and East Asian countries. The cooking process removed a further 61.6% of the ¹³⁷Cs activity relative to the activity in dressed fish. Taken together, this normal domestic fish dressing and culinary process removed 74.7% of the initial ¹³⁷Cs activity that had been present in the live fish. During the cooking, the radioactivity removed from the fish pieces was found to be distributed throughout the ingredients of the curry. The cooked pieces retained, on average, 38.5% of the radioactivity present in the raw dressed pieces. Among the ingredients, the gravy was found to contain an average of 34.8% of the activity of the dressed fish. The activity in greens and vegetables was found to vary from 4.0% (in cauliflower) to 7.2% (in potatoes). It may be concluded that normal home preparation and culinary processes removed much of the radioactivity from the fish.

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Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut^®) is a brain-protecting agent used clinically to treat acute ischemic stroke with a reaction mechanism of free radical scavenging. Since the initial stage of radiation damage involves the formation of free radicals, edaravone is expected to be effective in preventing lethal damage from ionizing radiation. In the present study, we used mice to examine in vivo the radioprotective effect of edaravone on whole body X-ray irradiation. A solution of edaravone was administered intraperitoneally to C3H mice (male, 10 weeks old), and they were irradiated with a total dose of 8.0 Gy. Edaravone exhibited dose-dependent and injection time-dependent radioprotection. When injected 30 min before the X-ray irradiation, it had the greatest radioprotective effect, whereas an injection after the irradiation showed no protective effect. The LD_50/30 was about 8.8 Gy for edaravone-injected mice and 6.6 Gy for control mice, yielding a DRF for edaravone (450 mg/kg bw) of 1.3. Edaravone decreased the body temperature transiently about 3–6C, but this did not seem to be responsible for the radioprotection. Since the radioprotection was observed only when the reagent was administered before the irradiation, the primary action of edaravone might be the quenching of free radicals with a short lifetime generated by the irradiation.

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Mushrooms are known to accumulate radiocesium. To estimate the intake of radiocesium through the eating of mushrooms, about 30 samples belonging to 4 commonly consumed species (Lentinula edodes, Hypsizigus marmoreus, Grifola frondosa, and Tricholoma matsutake), were analyzed for ¹³⁷Cs and ⁴⁰K. The concentration ranges were 0.060-29 Bq kg^-1 (wet wt) for ¹³⁷Cs and 38-300 Bq kg^-1 (wet wt) for ⁴⁰K. The geometric mean concentration for ¹³⁷Cs was 0.56 Bq kg^-1 (wet wt), and the mean concentration for ⁴⁰K was 92 Bq kg^-1 (wet wt). The ¹³⁷Cs concentrations in L. edodes cultivated in mushroom beds (sawdust-rice bran media) were lower than those cultivated on bed logs (natural wood with bark). The annual intake of ¹³⁷Cs per person through mushrooms was calculated, by using the current analytical results and food consumption data in Japan, to be 3.1 Bq for ¹³⁷Cs, which is about 28% of the total dietary intake of this nuclide. The effective dose equivalent of ¹³⁷Cs through mushrooms was estimated to be 4.0 ¤ 10^-8 Sv, which is about the half the value obtained in our previous study. The decrease of the ¹³⁷Cs intake through mushrooms is probably related to changes in cultivation methods in recent years, from the use of bed logs to mushroom beds.

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The p53 tumor-suppressor gene is one of the most frequently mutated genes in human cancers, and its genetic alterations may play critical roles in oncogenesis, tumor progression, and angiogenesis. To clarify the influence of the p53 status on hypoxia-inducible gene expression, we first performed transfection assays with a hypoxia-responsive vector carrying 5 hypoxia-responsive elements upstream of the human CMV minimal promoter driving transcription of the luciferase gene in various human tumor cell lines with wild-type (wt) or mutant (mut) p53. As a result, hypoxia responsiveness considerably varied between cell lines, and we could not obtain clear evidence that the hypoxia-inducible factor-1 (HIF-1) mediated gene expression in the wt-p53 cells was lower than that in cells with mut-p53. It is interesting that SaOS2 cells (p53 null) showed the highest luciferase activities under both aerobic and hypoxic conditions among tested cells. Next, to elucidate the effects of endogenous wt- and mut-p53s, a transfection assay and Northern blot analysis for VEGF transcription under hypoxia were performed by using isogenic variants of HT1080 cells differing in their p53 status. The luciferase and the endogenous VEGF mRNA expression were apparently lower in a variant carrying mutations in both p53 alleles than in a parental line harboring wt-p53, implying that some types of mutant p53 constitutively accumulated in cells can decrease both the basal and the hypoxia-induced expressions in addition to wt-p53.

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