Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: (1) reduction in number of apoptotic colonic crypt cells; (2) reduction in number of caspase-3 positive cells; (3) decreases in p53 accumulation and p21 expression; (4) decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region.

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Accidental radiation exposures or radiation therapy can cause internal and external damage including radiodermatitis. Even though radiodermatitis is one of the dose limiting factors in radiotherapy, the immunological nature of it is not yet been clearly understood. In this study, we have examined the alteration in immune cell population during the radiodermatitis process. A radiodermatitis model was established in HR-1 mice by locally exposing a posterior dorsal region to 10 Gy X-ray/day for 4 consecutive days. Collagen accumulation, redness, erythema, and dry desquamation of the skin were detected after X-irradiation. The size and total cell number of the spleen decreased immediately after X-irradiation, compared to those of the sham-irradiated mice, and recovered to the normal levels two weeks later. Reduction and recovery of the bone marrow cell population preceded a similar change of the spleen cell population. The proportion of CD4⁺ T cell increased, while the proportion of CD8⁺ T cell decreased ahead of the obvious skin damage, in both lymph node and spleen of the irradiated mice. Interestingly, the proportion of splenic monocytes/macrophages was expanded gradually at a similar kinetics with the aggravation of the radiodermatitis. The infiltration of the CD11b⁺ monocyte/macrophage to the X-irradiated skin also coincided with the development of radiodermatitis. These altered proportions of immune cells may play important roles in radiodermatitis.

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In the present study, using inhibitors of ceramide synthase (fumonisin B₁), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B₁ and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells.

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The EGS4 Monte Carlo simulation technique was used to obtain the energy spectra of photons arriving at a detector from the pulse height distributions measured by the same detector. First, the measured pulse height distribution for incident photons from several radiation sources such as ⁶⁰Co, ¹³⁷Cs, ¹⁵²Eu and ²⁰⁷Bi with a collimator are compared with those calculated using the EGS4 code to investigate the feasibility of the simulation. The comparison showed good agreement of 98.7% for ⁶⁰Co, 92.5% for ²⁰⁷Bi on the total counts. Second, the pulse height distributions were measured in the open space and then unfolded. The measurement of the distributions was done with changing the source to detector distance (SDD) from 10 cm to 100 cm for ⁶⁰Co and ¹³⁷Cs respectively. In the unfolding process, response functions of a high purity Ge (HPGe) detector were calculated using the EGS4 code. The calculated pulse height distributions were then normalized to the measured ones at the peaks of the incident photon energies. The ratio of the sum of counts of the main peaks to the total count in the unfolded spectra for ⁶⁰Co varied from 5.4 to 5.7 times greater than those in the measured pulse height distributions, while from 2.5 to 2.9 times for ¹³⁷Cs. Electron contribution to the unfolded spectra for ¹³⁷Cs decreased as the source to detector distance increased, becoming negligible above 50 cm. The pulse height distributions at the center of the reference plane at 100 cm from the ⁶⁰Co and ¹³⁷Cs dummy sources located inside each irradiator were also measured and unfolded to obtain the real pulse height distribution. In the unfolded spectra, the photons scattered from the surrounding materials were reduced to approximately one fourth of those measured in the open space due to the small size of apertures of the irradiators. The ratio of the sum of counts for the main peaks to the total count was larger than those in the measured pulse height distributions by the factor of 5.0 for ⁶⁰Co and 3.4 for ¹³⁷Cs. The uncertainties estimated in the unfolding processes were around 0.1% for ⁶⁰Co and 0.07% for ¹³⁷Cs.

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To evaluate the relative biological effectiveness (RBE) of low doses of neutrons on fetal nervous development, [C57BL/6J × C3H/He] hybrid (B6C3F1) mice were exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02-1.0 Gy) or ¹³⁷Cs-generated gamma-rays (0.1-2.0 Gy) on embryonic day 13.5. We then evaluated the incidence of neuronal apoptosis in the cerebral cortex 24 hours after irradiation. Neuronal apoptosis increased in a dose-dependent manner in both neutron-and gamma-ray-irradiated groups: even at the lowest dose, a minimal increase in the apoptotic index was noted in response to both types of radiation. The dose-response curves were best fitted to linear quadratic models, and the evaluated RBE was 9.8, which was considered to be large for a prenatal effect and acute tissue injury induced by a low dose of neutrons.

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The present article describes the series of incident primary ovarian tumors in the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation, with particular emphasis on case ascertainment and characterization of histological features of the tumors. We identified 723 ovarian tumors (260 malignant, 463 benign) in 648 individuals of about 70,000 female LSS subjects; 71 cases had more than one ovarian tumor. We histologically confirmed 601 tumors (182 malignant, 419 benign tumors). The most frequent histological type was common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The distributions of ovarian tumors by histological type were similar to those from other studies. Among malignancies, the frequency of common epithelial types relative to other tumor types increased with radiation dose (p = 0.02). Among benign tumors, the relative frequency of sex-cord stromal tumors increased with radiation dose (p = 0.04). The women with mucinous cancer had better survival than those with serous cancers (p = 0.03). Within tumor types, there was no consistent pattern of survival by radiation dose. Variations in histological types of ovarian tumors in response to radiation dose, suggested by the case series data need to be followed up by population-based incidence analysis.

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We studied the cytoprotective effect of triphlorethol-A against γ-ray radiation- induced oxidative stress. In this study, hydrogen peroxide, which is a reactive oxygen species (ROS), was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) assay. Triphlorethol-A reduced intracellular hydrogen peroxide generated by γ-ray radiation. This compound provided protection against radiation-induced membrane lipid peroxidation and cellular DNA damage which are the main targets of radiation-induced damage. Triphlorethol-A protected the cell viability damaged by the radiation through inhibition of apoptosis. Triphlorethol-A reduced the expression of bax and activated caspase 3 induced by radiation, but recovered the expression of bcl-2 decreased by radiation. Taken together, the results suggest that triphlorethol-A protects cells against oxidative damage induced by radiation through reducing ROS.

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The paper describes the development of chemical modules simulating the prechemical and chemical stages of charged particle tracks in pure liquid water. These calculations are based on our physical track structure codes for electrons and ions (KURBUC, LEPHIST and LEAHIST) which provide the initial spatial distribution of H₂O⁺, H₂O^* and subexcitation electrons at ~10^-15 s. We considered 11 species and 26 chemical reactions. A step-by-step Monte Carlo approach was adopted for the chemical stage between 10^-12 s and 10^-6 s. The chemistry codes enabled to simulate the non-homogeneous chemistry that pertains to electron, proton and alpha-particle tracks of various linear energy transfers (LET). Time-dependent yields of chemical species produced by electrons and ions of different energies were calculated. The calculated primary yields (G values at 10^-6 s) of 2.80 for OH and 2.59 for e^-_aq for 1 MeV electrons are in good agreement with the published values. The calculated G values at 10^-6 s for a wide range LETs from of 0.2 to 235 keVμm^-1 were obtained. The calculations show the LET dependence for OH and H₂O₂. The electron penetration ranges were calculated in order to discuss the role of low energy electrons.

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Thermoresistant (TR) clone of radiation-induced fibrosarcoma (RIF) cells have been reported to show adaptive response to 1cGy of low dose radiation, and hsp25 and inducible hsp70 are involved in this process. In the present study, to further elucidate the mechanism of how hsp25 and inducible hsp70 regulate the adaptive response, hsp25 or inducible hsp70 overexpressed RIF cells were irradiated with 1cGy and cell cycle was analyzed. Hsp25 or inducible hsp70 overexpressed cells as well as TR cells showed increase of G1 phase population after γ-irradiation at 1cGy, while the parent RIF cells did not. [³H]-Thymidine and BrdU incorporation also indicated that both hsp25 and inducible hsp70 were involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in hsp25 and inducible hsp70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of adaptive response by hsp25 and inducible hsp70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest.

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The aim of this study was to determine the effects of vitamin E (VE) and L-carnitine (LC) supplementation, separately or in combination, on radiation-induced oral mucositis and myelosuppression. Group 1 received no treatment (control). Group 2 received 15 Gray of ⁶⁰Co gamma irradiation as a single dose to total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE (IR+VE) or 200 mg/kg/day LC (IR+LC) or in combination (IR+VE+LC) respectively. Clinically and histopathologically, assessments of mucosal reactions were performed by two independent experts in Radiation Oncology and Pathology, respectively. Hematologic analyses and antioxidant enzyme evaluations were also performed. Irradiation significantly increased oral mucositis, and decreased thrombocyte and White Blood Cell counts. A significant increase in malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and catalase (CAT) activities in plasma were found in the IR group. VE and LC administration, separately, plus irradiation significantly delayed the starting day, and reduced the severity of, oral mucositis. This administration also reduced a fall in the numbers of thrombocyte and WBC caused by irradiation, and decreased the MDA level, and increased the activity of SOD and CAT enzymes in the plasma. VE and LC, in combination, plus irradiation did not provide a superior radioprotection against radiation-induced toxicities.

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