Showing papers in "Journal of Radiation Research in 2000"
TL;DR: The mortality of all cancers in HBRA was generally lower than that in the control area, but not statistically significant, and neither homogeneity tests nor trend tests revealed any statistically significant relationship between cancer risk and radiation dose.
Abstract: The objective of the present study was to estimate cancer risk associated with the low-level radiation exposure of an average annual effective dose of 6.4 mSv (including internal exposure) in the high background-radiation areas (HBRA) in Yangjiang, China. The mortality survey consisted of two steps, i.e., the follow-up of cohort members and the ascertainment of causes of death. The cohort members in HBRA were divided into three dose-groups on the basis of environmental dose-rates per year. The mortality experiences of those three dose groups were compared with those in the residents of control areas by means of relative risk (RR). During the period 1987-1995, we observed 926,226 person-years by following up 106,517 subjects in the cohort study, and accumulated 5,161 deaths, among which 557 were from cancers. We did not observe an increase in cancer mortality in HBRA (RR = 0.96, 96% CI, 0.80 to 1.15). The combined data for the period 1979-95 included 125,079 subjects and accumulated 1,698,316 person-years, observed 10,415 total deaths and 1,003 cancer deaths. The relative risk of all cancers for whole HBRA as compared with the control area was estimated to be 0.99 (95% CI, 0.87 to 1.14). The relative risks of cancers of the stomach, colon, liver, lung, bone, female breast and thyroid within whole HBRA were less than one, while the risks for leukemia, cancers of the nasopharynx, esophagus, rectum, pancreas, skin, cervix uteri, brain and central nervous system, and malignant lymphoma were larger than one. None of them were significantly different from RR = 1. Neither homogeneity tests nor trend tests revealed any statistically significant relationship between cancer risk and radiation dose. We did not find any increased cancer risk associated with the high levels of natural radiation in HBRA. On the contrary, the mortality of all cancers in HBRA was generally lower than that in the control area, but not statistically significant.
107 citations
TL;DR: Exposure to the high density ELFMF at more than 50 mT may potentiate X-ray-induced DNA strand breaks in human glioma MO54 cells.
Abstract: We examined the effect of an extremely low-frequency magnetic field (ELFMF) at 5, 50 and 400 mT on DNA strand breaks in human glioma MO54 cells. A DNA damage analysis was performed using the method of alkaline comet assay. The cells were exposed to X-rays alone (5 Gy), ELFMF alone, or X-rays followed by ELFMF at 4 degrees C or on ice. No significant difference in the tail moment was observed between control and ELFMF exposures up to 400 mT. X-ray irradiation increased DNA strand breaks. When cells were exposed to X-rays followed by ELFMF at 50 and 400 mT, the tail moment increased significantly compared with that for X-rays alone. When the exposure of cells was performed at 37 degrees C, no significant change was observed between X-rays alone and X-rays plus 400 mT. We previously observed that exposure to 400 mT ELFMF for 2 h increased X-ray-induced mutations (Miyakoshi et al, Mutat. Res., 349: 109-114, 1996). Additionally, an increase in the mutation by exposure to the ELFMF was observed in cells during DNA-synthesizing phase (Miyakoshi et al., Int. J. Radiat. Biol., 71: 75-79, 1997). From these results, it appears that exposure to the high density ELFMF at more than 50 mT may potentiate X-ray-induced DNA strand breaks.
78 citations
TL;DR: A historical overview of the studies before the cooperation and the first two phases of the cooperative project involving both Chinese and Japanese scientists is presented.
Abstract: The epidemiological study on the residents of the high background radiation areas in Yangjiang, China was started by Chinese scientists in 1972 and continued until 1986. In 1991, Japanese scientists recognized the importance of the work and a joint feasibility study was conducted with revised protocols. The feasibility study matured to a cooperative project involving both Chinese and Japanese scientists in 1992, which currently is still in progress. The project was divided into three phases; the first being from 1992 to 1995, the second from 1995-1998 and the third from 1998 to 2001. The results of the first phase were reported previously in 1996. The present paper is a historical overview of the studies before the cooperation and the first two phases. Remarks are made on the detailed data on dosimetry, cytogenetic studies and cancer epidemiology of a series of the papers in this supplemental issue. Some problems such as paradoxical observations between cytogenetic results and cancer mortality, and the importance of the high background study in risk assessment are discussed.
68 citations
TL;DR: The results strongly suggest that the target for both types of cell death is the same, as the RBE values calculated from the initial slope for both apoptosis and reproductive death were found.
Abstract: Apoptosis/Heavy-ion/LET/RBE/V79 cells We investigated the relationship between the LET values and cell death, defined as either apoptosis or loss of reproductive integrity (reproductive death), using Chinese hamster V79 cells. The cells were irradiated with X-rays or carbon-ion beams from the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS). Apoptosis was defined based on the morphological change upon treating of cells with caffeine. The apoptotic index, the ratio of apoptotic cells to the total, after exposure to 2 Gy of X-rays was 0.043. Upon irradiation with carbon-ion beams, the index was gradually increased with increasing LET values, reaching a maximum of 0.076 at 110 keV/ µm, and then decreased to 0.054 at 237 keV/µm. An analogous pattern of the LET dependence was observed between reproductive death and apoptotic death. The cell-survival values obtained after 2 Gy exposure (SF2) were 0.64, 0.13, and 0.24, respectively. A similar trend was found for the RBE values calculated from the initial slope for both apoptosis and reproductive death. These results strongly suggest that the target for both types of cell death is the same.
67 citations
TL;DR: Univariate conditional logistic regression analysis showed that NPC risk was associated with the consumption of salted fish, homemade pickles, and fermented soy beans, education levels, the history of chronic rhinitis, and the family history of NPC.
Abstract: The main purposes of this study were to identify the major determinants of nasopharyngeal carcinoma (NPC) in the high-background radiation areas (HBRA) in Yangjiang, China and to evaluate their potential confounding effects on the NPC risk associated with exposure to high background radiation. A matched case-control study was conducted using those who died of NPC during the period 1987-1995. Two controls were randomly selected for each case from those who died from causes other than malignancies and external causes. Cases and their controls were matched with respect to sex and the years of birth and death (+/- 5 years). Study subjects' next-of-kin were interviewed using a standardized questionnaire to collect information on socioeconomic status, dietary habits, tobacco smoking and alcohol consumption, disease history, pesticide use, medical X-ray exposure, the family history of NPC and so on. We succeeded in interviewing 97 cases and 192 controls. Univariate conditional logistic regression analysis showed that NPC risk was associated with the consumption of salted fish, homemade pickles, and fermented soy beans, education levels, the history of chronic rhinitis, and the family history of NPC. Multivariate conditional logistic regression analysis revealed that education levels (Odds ratio (OR) for middle school or higher levels vs. no school education = 3.8, 95% CI = 1.2 to 11.8), salted fish intake (OR = 3.2, 95% CI = 1.7 to 6.1), the history of chronic rhinitis (OR = 3.6, 95% CI = 1.3 to 10.1), and the family history of NPC (OR = 14.2, 95% CI = 2.7 to 73.4) were independent risk factors of NPC. Tobacco smoking (OR = 1.2, 95% CI = 0.7 to 2.1), and alcohol consumption (OR = 0.9, 95% CI = 0.5 to 1.9) were not significantly related to NPC risk. The ORs of NPC risk comparing HBRA and a nearby control area before and after adjustment for the major risk determinants identified in the present study were 0.86 (95% CI = 0.50 to 1.50) and 0.87 (95% CI = 0.45 to 1.67), respectively. Salted fish intake was a strong risk factor of NPC. Education, the history of chronic rhinitis and the family history of NPC were also related to NPC risk. The exposure to high background radiation in HBRA of Yangjiang was not related to NPC risk with or without the adjustment for those major risk determinants of NPC.
58 citations
TL;DR: The frequency of Dic + Rc linearly increases over lifetime due to chronic low dose exposure and it is likely that the activation of repair enzymes is not triggered in the present HBRA, and Threshold dose of the induction of chromosome aberrations, if any, is below the present dose level.
Abstract: Chromosomes of 39 healthy family members (3 generations from 13 families) living both in the high-level background radiation areas (HBRA) and the control areas (CA) were studied. Cumulative dose from birth to the time of blood sampling was estimated by calculating measured exposure rate in each individual. The cumulative doses ranged 30.9-358.9 and 6.0-59.2 mGy for HBRA and CA, respectively. Peripheral lymphocyte chromosome preparations were made according to our improved method. Dicentric and ring chromosomes (Dic + Rc) were scored in average 2,527 cells per individual in HBRA and 2,694 cells in CA under a microscope equipped with an automated stage. A positive correlation between Dic + Rc and age was found in HBRA, while no such dose relationship was clear in CA. The frequency of Dic + Rc linearly increases over lifetime due to chronic low dose exposure and it is likely that the activation of repair enzymes is not triggered in the present HBRA. Threshold dose (rate) of the induction of chromosome aberrations, if any, is below the present dose (rate) level.
48 citations
Journal Article•
TL;DR: It is concluded that the Nth, Nei, and MutM proteins are involved in the repair pathways for 5-foU that serve to avoid mutations in E. coli.
39 citations
TL;DR: The results clearly demonstrate the superiority of the glass Dosimetry regarding simplicity of operation, stability of long-term dose accumulation and good detector uniformity, which allow accurate tissue dosimetry.
Abstract: A photoluminescence glass dosimeter, GD-301, was applied to the measurement of low absorbed doses in mice exposed to low-dose rate 137Cs gamma-rays. The dosimeter system consists of small rod-shaped glass chip detectors capable of embedded in the body of a mouse and an automatic readout device equipped with a standard detector irradiated with 137Cs gamma-source. The measured absorbed doses were compared with the "exposure" estimated by an ionization chamber and with the doses measured by a BeO:Na thermoluminescence system. The results clearly demonstrate the superiority of the glass dosimetry regarding simplicity of operation, stability of long-term dose accumulation and good detector uniformity, which allow accurate tissue dosimetry.
38 citations
TL;DR: In p53(+/+) mice, there was no difference in the induced rate per Gy of reduction in the surviving fraction of lymphocytes between acute (0.4 Gy/min) and chronic gamma-irradiations, indicating that radiation-induced apoptosis in lymphocytes is a dose-rate independent event.
Abstract: RBE of fission neutrons/Dose-rate independent apoptosis/Thymus atrophy/p53/Hyperplasia Following the exposure of mice to X rays or fission neutrons, the frequency (F) of apoptosis was measured after 4 h, and the weight loss or lymphocyte content loss in the thymus and spleen was measured after 24 h. In p53(+/+) mice, F increased linearly with the dose (D (Gy)) and the induced rate per Gy of F (detected by TUNEL staining) was 0.05 and 0.23 for X rays and fission neutrons, respectively. Therefore, the RBE of fission neutrons was 4.6 for apoptosis induction. This indicates that radiationinduced apoptosis is mostly due to double strand breaks (DSBs) in DNA because we previously obtained almost the same RBE value of fission neutrons for the induction of crossover mutations in Drosophila melanogaster, which arise from the recombinational repair of DSBs. In p53(+/+) mice, decreases in the organ weight and the lymphocyte content were observed for the thymus and the spleen 24 h after X-irradiation. These atrophic changes in the thymus and the spleen quantitatively corresponded to the total apoptotic cell deaths occurring in them. However, in p53(–/–) mice, no vigorous apoptosis was induced after X-irradiation, and hyperplastic changes in the weight and the lymphocyte content appeared in the thymus and the spleen 24 h after X-irradiation. In p53(+/+) mice, there was no difference in the induced rate per Gy of reduction in the surviving fraction of lymphocytes between acute (0.4 Gy/min) and chronic (3 mGy/min) γ-irradiations. Namely, radiation-induced apoptosis in lymphocytes is a dose-rate independent event.
38 citations
Journal Article•
TL;DR: Exposure to 5 mT ELFMF may induce mutations and enhance X-ray-induced mutations, resulting from the inactivation of NF-kappaB through the inhibition of tyrosine phosphorylation, as well as enhancing mutations induced by X-rays.
Abstract: It is established that extremely low frequency magnetic fields (ELFMF) at the flux densities, i.e., 5 mT and less, are not mutagenic. However, exposure to ELFMF enhances mutations induced by X-rays. In this study, we examined the effects of long-term exposure to 5 mT ELFMF on mutation induction and X-ray-induced mutations in human malignant glioma cells (MO54) with different mutant IkappaB-alpha (a critical inhibitor of NF-kappaB) genes. Cells were exposed or sham-exposed to 5 mT ELFMF for up to 8 days with or without initial X-rays (4 Gy), and the mutant frequency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene was analyzed. An obvious increase in X-ray-induced mutations was observed after treatment with ELFMF in combination with X-irradiation in MO54 cells with tyrosine mutant IkappaB-alpha gene other than with serine mutant IkappaB-alpha gene or vector alone. Exposure to ELFMF alone increased mutations significantly in MO54 cells with tyrosine mutant IkappaB-alpha gene. In addition, X-ray-induced apoptoic cells were increased in MO54-V cells after exposure to ELFMF, while an anti-apoptotic effect of magnetic field was found in MO54-SY4 cells. Our data suggest that exposure to 5 mT ELFMF may induce mutations and enhance X-ray-induced mutations, resulting from the inactivation of NF-kappaB through the inhibition of tyrosine phosphorylation.
35 citations
TL;DR: The positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, are recommended, which recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population.
Abstract: From 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966-96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women. The age of the patients varied from 15 to 90 years. Overall, a diagnosis of adenomatous goiter (most frequently multinodular) was found in 1683 patients (63.4%) of Semipalatinsk region, in 2032 patients (68.6%) of Ust-Kamenogorsk region and in 1142 patients (69.0%) of Pavlodar region. In the period 1982-96, as compared before, there was a noticeable increase in the number of cases of Hashimoto's thyroiditis and thyroid cancer. Among histological forms of thyroid cancer, papillary (48.1%) and follicular (33.1%) predominated in the Semipalatinsk region. In later periods (1987-96), an increased frequency of abnormal cases occurred among patients less than 40 years of age, with the highest proportion among patients below 20 in Semipalatinsk and Ust-Kamenogorsk regions of Kazakstan. Given the positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, we recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population.
TL;DR: Improved chromosome-painting methods for accurate judgment of dicentrics and translocations are introduced and the practicality of these advanced cytogenetic techniques is shown by examinations of individuals exposed in the radiation accident at Tokaimura in 1999.
Abstract: The frequency of chromosome aberrations in circulating lymphocytes is accepted as being the most reliable indicator of the absorbed dose of radiation. Researches done to improve the accuracy of cytogenetic analysis are described in this review. These include investigations of in vitro factors that affect the yield of radiation-induced aberrations and of in vivo factors that affect the chromosomal radiosensitivity of individuals. Improved chromosome-painting methods for accurate judgment of dicentrics and translocations are introduced. The practicality of these advanced cytogenetic techniques is shown by examinations of individuals exposed in the radiation accident at Tokaimura in 1999.
TL;DR: This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.
Abstract: In order to investigate an association between residential radon exposure and risk of lung cancer, a case-control study was conducted in Misasa Town, Tottori Prefecture, Japan. The case series consisted of 28 people who had died of lung cancer in the years 1976-96 and 36 controls chosen randomly from the residents in 1976, matched by sex and year of birth. Individual residential radon concentrations were measured for 1 year with alpha track detectors. The average radon concentration was 46 Bq/m3 for cases and 51 Bq/m3 for controls. Compared to the level of 24 or less Bq/m3, the adjusted odds ratios of lung cancer associated with radon levels of 25-49, 50-99 and 100 or more Bq/m3, were 1.13 (95% confidence interval; 0.29-4.40), 1.23 (0.16-9.39) and 0.25 (0.03-2.33), respectively. None of the estimates showed statistical significance, due to small sample size. When the subjects were limited to only include residents of more than 30 years, the estimates did not change substantially. This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.
TL;DR: Functional analysis of the NBS1 protein is in progress and it should provide further clues to understanding the repair mechanism of radiation-induced DNA double-strand breaks, a crucial factor in DNA repair.
Abstract: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, combined immunodeficiency, and a high incidence of lymphoid tumor. Cells from NBS patients show chromosomal instability, hypersensitivity to ionizing radiation and abnormal p53-mediated cell cycle regulation. We cloned the underlying gene for NBS, designated NBS1, by complementation-assisted positional cloning from the candidate region 8q21. Large genomic sequencing, as well as a search using computer programs, provides a powerful approach for identifying the underlying gene for a disease. The NBS1 gene encodes a protein of 754 amino acids that has FHA and BRCT domains which often are conserved in cell-cycle checkpoint proteins. The gene has weak homology to the yeast (Saccharomyces cerevisiae) Xrs2 protein in the N-terminus region. Like yeast Xrs2, the NBS1 protein forms a complex with hRAD50/hMRE11, and the complex is condensed as foci in the nucleus after irradiation, indicative that this triple-complex is a crucial factor in DNA repair. Functional analysis of the NBS1 protein is in progress and it should provide further clues to understanding the repair mechanism of radiation-induced DNA double-strand breaks.
TL;DR: The high incidence of micronuclei in lymphocytes in residents of the Semipalatinsk nuclear test site area was mainly caused by internal exposure rather than external exposure received for the past 40 years.
Abstract: Semipalatinsk/ Micronucleus test/ Low dose exposure/Biological dosimetry/ Nuclear explosion test The Semipalatinsk area is highly contaminated with radioactive fallout from 40 years of continuous nuclear testing. The biological effects on human health in this area have not been studied. Significant remaining radioactivities include long-lived radioisotopes of 238, 239, 400 Pu, 137 Cs and 90 Sr. To evaluate the long-term biological effects of the radioactive fallout, the incidence of micronuclei in lymphocytes from residents of the area was observed. Blood was obtained from 10 residents (5 females and 5 males, aged 47 to 55 years old) from each of the 3 areas of Znamenka, Dolon and Semipalatinsk, which are about 50 ‐150 km from the nuclear explosion test site. For micronucleus assay, PHA-stimulated lymphocytes were cultured for 72 h and cytochalasin B was added at 44 h for detecting binuclear lymphocytes. Five thousand binuclear lymphocytes in each resident were scored. The means of micronucleus counts in 1,000 lymphocytes in residents of Semipalatinsk, Dolon and Znamenka were 16.3, 12.6, and 7.80, respectively, which were higher than those of the normal Japanese persons (4.66). These values were equivalent to the results obtained from 0.187‐0.47 Gy of chronic exposure to γ-rays at a dose rate of 0.02 cGy /m in. The high incidence of micronuclei in residents of the Semipalatinsk nuclear test site area was mainly caused by internal exposure rather than external exposure received for the past 40 years.
TL;DR: The presence of a novel DNA repair enzyme in R. radiotolerans cells that recognizes radiation-induced DNA damages such as thymine glycol, urea residues, and abasic sites is demonstrated and suggests that R-endonuclease is a functional homolog of endonuclease III of Escherichia coli.
Abstract: Rubrobacter radiotolerans is an extremely radioresistant bacterium. It exhibits higher resistance than the well-known radioresistant bacterium Deinococcus radiodurans, but the molecular mechanisms responsible for the radioresistance of R. radiotolerans remain unknown. In the present study, we have demonstrated the presence of a novel DNA repair enzyme in R. radiotolerans cells that recognizes radiation-induced DNA damages such as thymine glycol, urea residues, and abasic sites. The enzyme was purified from the crude cell extract by a series of chromatography to an apparent physical homogeneity. The purified enzyme showed a single band with a molecular mass of approximately 40 kDa in SDS-polyacrylamide gel electrophoresis, and was designated as R-endonuclease. R-Endonuclease exhibited repair activity for thymine glycol, urea residues, and abasic sites present in plasmid DNA, but did not act on intact DNA, UV-irradiated DNA and DNA containing reduced abasic sites. The substrate specificity together with the salt and pH optima suggests that R-endonuclease is a functional homolog of endonuclease III of Escherichia coli.
TL;DR: It is proposed that by combining hypoxia-selective gene delivery with hypoxIA-specific gene expression and oxygen-sensitive prodrug activation, radioresistant hypoxic tumour tissues may be effectively targeted.
Abstract: Studies have shown that reduced oxygen tension (hypoxia) in solid tumours adversely affects the outcome of radiotherapy. Despite being an independent prognostic marker of poor treatment outcome, hypoxia represents a physiological difference that can be utilised for selective cancer treatment. Since severe hypoxia (pO2<0.3%; 2.5 mmHg) does not occur in normal tissue, it may be exploited for therapeutic gain. Accurate targeting of oxygen-deprived cells within a tumour mass may be achieved using hypoxia-targeted gene therapy. For gene therapy three separate issues need to be considered: 1) delivery of a gene to the tumour, 2) regulation of gene expression and 3) therapeutic efficacy. Each of these aspects is outlined here, with a view to gene therapy of the hypoxic tumour environment. It is proposed that by combining hypoxia-selective gene delivery with hypoxia-specific gene expression and oxygen-sensitive prodrug activation, radioresistant hypoxic tumour tissues may be effectively targeted.
TL;DR: Analysis of kinetics of the expression of intercellular adhesion molecule-1 and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer suggests that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation- induced colonic ulcer.
Abstract: Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting. ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer.
TL;DR: The effect of radiation on the induction of chromosome aberrations seems to be less significant than those of metabolic factors and/or mutagenic agents (excluding radiation) even in HBRA in China.
Abstract: We performed a cytogenetical study using chromosome painting analysis on 9 residents of the naturally high background radiation areas (HBRA) and 8 residents of the control areas in southern China. The estimated dose (air kerma) of each resident measured by an electric pocket dosimeter showed 2.20-4.23 mGy/year in HBRA and 0.56-0.70 mGy/year in the control areas. A total of 14,096 cells (1,566 cells/case) in the former and 17,522 cells (2,190 cells/case) in the latter were analyzed. Children, both in HBRA and in the control areas, had translocations at low frequencies. The frequency of translocations among elder individuals varied widely and it was not possible to detect dose effect although it was detected in dicentrics. The effect of radiation on the induction of chromosome aberrations, which have a statistically potential risk of causing malignant or congenital diseases, seems to be less significant than those of metabolic factors and/or mutagenic agents (excluding radiation) even in HBRA in China.
TL;DR: How the indirect estimation was made on individual dose and the methodology used to estimate radiation risk were described are described and the excess relative risks of four leading cancers in the study areas are estimated.
Abstract: A study was made on cancer mortality in the high-background radiation areas of Yangjiang, China. Based on hamlet-specific environmental doses and sex- and age-specific occupancy factors, cumulative doses were calculated for each subject. In this article, we describe how the indirect estimation was made on individual dose and the methodology used to estimate radiation risk. Then, assuming a linear dose response relationship and using cancer mortality data for the period 1979-1995, we estimate the excess relative risk per Sievert for solid cancer to be -0.11 (95% CI, -0.67, 0.69). Also, we estimate the excess relative risks of four leading cancers in the study areas, i.e., cancers of the liver, nasopharynx, lung and stomach. In addition, we evaluate the effects of possible bias on our risk estimation.
TL;DR: The enhancement of the ESR signal decay of carbamoyl-PROXYL due to X-irradiation was suppressed by a treatment with all of the radioprotectors examined, showing positive SI values, suggesting that several mechanisms exist for Radioprotection and a modification of the signal decay rate.
Abstract: Previously, we reported that X-irradiation enhanced the signal decay of a spin probe injected into whole mice measured by in vivo ESR, and that the observed enhancement was suppressed by the preadministration of cysteamine, a radioprotector [Miura, Y., Anzai, K., Urano, S. and Ozawa, T. (1997) Free Rad. Biol. Med. 23: 533‐540]. In the present study, the suppression activity of the X-ray-induced increase in the ESR signal decay rate (termed suppression index, SI) was measured for several radioprotectors: 5-hydroxytryptamine (5-HT), S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721), 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (TEMPOL), cimetidine, interleukin-1β (IL-1β) and stem cell factor (SCF). The enhancement of the ESR signal decay of carbamoyl-PROXYL due to X-irradiation was suppressed by a treatment with all of the radioprotectors examined, showing positive SI values. However, a dose-dependency of 5-HT or WR-2721 was not observed, suggesting that several mechanisms exist for radioprotection and a modification of the signal decay rate. Although the in vivo ESR system cannot be used in place of the 30-day survival method for the assessment of radioprotectors, this system might be applicable to in vivo, non-invasive screening prior to using the 30day survival method.
TL;DR: In the present system radiosensitization by wortmannin was also at least partly mediated through enhancement of apoptotic cell death, which suggests a possible role of certain protein kinases, such as DNA-PK and/or ATM among PI3-kinase family.
Abstract: Here we found that wortmannin sensitized Chinese hamster V79 cells to hyperthermic treatment at 44.0 degrees C as determined either by colony formation assay or by dye exclusion assay. Wortmannin enhanced heat-induced cell death accompanying cleavage of poly (ADP-ribose) polymerases (PARP). Additionally, the induction of heat shock protein HSP70 was suppressed and delayed in wortmannin-treated cells. Heat sensitizing effect of wortmannin was obvious at more than 5 or 10 microM of final concentrations, while radiosensitization was apparent at 5 microM. Requirement for high concentration of wortmannin, i.e., order of microM, suggests a possible role of certain protein kinases, such as DNA-PK and/or ATM among PI3-kinase family. The sensitization was minimal when wortmannin was added at the end of heat treatment. This was similar to the case of X-ray. Since heat-induced cell death and PARP cleavage preceded HSP70 induction phenomenon, the sensitization to the hyperthermic treatment was considered mainly caused by enhanced apoptotic cell death rather than secondary to suppression or delay by wortmannin of HSP70 induction. Further, in the present system radiosensitization by wortmannin was also at least partly mediated through enhancement of apoptotic cell death.
TL;DR: A dose-assessment study to evaluate the external exposure to natural radiation in the high background radiation areas of Yangjiang in Guangdong province and in the control areas of Enping prefecture since 1991 found that the occupancy factor was higher for infants and aged individuals than for other age groups, leading to higher dose rates of exposure to those age groups.
Abstract: As a part of the China-Japan cooperative research on natural radiation epidemiology, we have carried out a dose-assessment study to evaluate the external exposure to natural radiation in the high background radiation areas (HBRA) of Yangjiang in Guangdong province and in the control areas (CA) of Enping prefecture since 1991. Because of the difficulties in measuring the individual doses of all inhabitants directly by personal dosimeters, an indirect method was applied in which the exposed individual doses were estimated from the environmental radiation doses measured by survey meters and the occupancy factors of each hamlet. We analyzed the dose in the hamlets and the variation in the occupancy factors to obtain the parameters of dose estimation on the inhabitants in selected hamlets; Madi and several hamlets of different dose levels in HBRA and Hampizai hamlet in CA. With these parameters, we estimated individual dose rates and compared them with those obtained from direct measurement using dosimeters carried by selected individuals. The results obtained are as follows. 1) The environmental radiation doses are influenced by the natural radioactive nuclide concentrations in building materials, the age of the building and the arrangement of the houses in a hamlet. There existed a fairly large and heterogeneous distribution of indoor and outdoor environmental radiations. The indoor radiation doses were due to exposure from the natural radioactive nuclides in the building materials and were about two times as large as the outdoor radiation doses. The difference between indoor and outdoor doses was not observed in CA. 2) The occupancy factor was influenced by the age of individuals and by the season of the year. The occupancy factor was higher for infants and aged individuals than for other age groups. This lead to higher dose rates of exposure to those age groups. 3) A good correlation was observed between the dose assessed indirectly and that measured directly and the correlation factor was 0.97.
TL;DR: Findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus.
Abstract: The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telencephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus.
TL;DR: Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine labeling index and mitotic index than control and none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest.
Abstract: To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD50/60) was 42.2 +/- 0.25 Gy (standard error) for X-rays, and 22.7 +/- 0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD50/60. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure.
TL;DR: It is suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells.
Abstract: To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells.
TL;DR: The results strongly suggest that the collapse of delta psi m is not a part of the central apoptotic machinery, and that caspase cascade(s), especially caspases-8 to -3, play an important role in UVC-induced apoptosis in A431.
Abstract: Human epidermoid tumor A431 cells underwent apoptosis following exposure to ultraviolet C (UVC). The apoptosis was of the interphase death type, and mostly occurred within one cell cycle, independent of the cell-cycle phases. We further examined the detailed sequential order of apoptotic changes in cells after UVC exposure and the involvement of caspases using six caspase inhibitors. The loss of mitochondrial transmembrane potential (delta psi m) appeared in the earliest phase; subsequently, the chromatin condensation and DNA-fragmentation occurred. Cell shrinkage and loss of the plasma-membrane integrity, judged by propidium iodide (PI) staining, were observed in the later phase. A broad-spectrum caspase inhibitor, z-VAD-fmk, completely prevented all apoptotic changes, except for the depletion of delta psi m. Both Ac-DEVD-CHO and Ac-IETD-CHO, inhibitors of caspase -3 and -8, respectively, effectively inhibited typical chromatin condensation to almost the same extent. However, the nuclei still showed partial condensation. A caspase -9 inhibitor, Ac-LEHD-CHO, did not prevent chromatin condensation, though it partially inhibited cell-size reduction and PI-stainability. None of the caspase inhibitors could inhibit the delta psi m reduction. These results strongly suggest that the collapse of delta psi m is not a part of the central apoptotic machinery, and that caspase cascade(s), especially caspase-8 to -3, play an important role in UVC-induced apoptosis in A431.
TL;DR: The findings indicated that the effects of both carbon-ion irradiation and X-irradiation on the development of rat brain are similar in character, and the effect of 1.5 Gy carbon-ions irradiation compares to that of 2.0-2.0 Gy X-radiation.
Abstract: The effects of carbon-ion irradiation and X-irradiation on the development of rat brain were compared. Twenty pregnant rats were injected with bromodeoxyuridine (BrdU) at 9 pm on day 18 of pregnancy and divided into five groups. Three hours after injection (day 19.0) one group was exposed to 290 MeV/u carbon-ion radiation by a single dose of 1.5 Gy. Other groups were exposed to X-radiation by 1.5, 2.0 or 2.5 Gy, or sham-treated, respectively. Fetuses were removed from one dam in each group 8 h after exposure and examined histologically. Extensive cell death was observed in the brain mantle from the irradiated groups. The cell death after 1.5 Gy carbon-ion irradiation was remarkably more extensive than that after 1.5 Gy X-irradiation, but comparable to that after 2.0 Gy or 2.5 Gy X-irradiation. The remaining rats were allowed to give birth and the offspring were sacrificed at 6 weeks of age. All of the irradiated offspring manifested microcephaly. The size of the brain mantle exposed to 1.5 Gy carbon-ion radiation was significantly smaller than that exposed to 1.5 Gy X-radiation and larger than that exposed to 2.5 Gy X-radiation. A histological examination of the cerebral cortex revealed that cortical layers II-IV were malformed. The defect by 1.5 Gy carbon-ion irradiation was more severe than that by the same dose of X-irradiation. Although the BrdU-incorporated neurons were greatly reduced in number in all irradiated groups, these cells reached the superficial area of the cortex. These findings indicated that the effects of both carbon-ion irradiation and X-irradiation on the development of rat brain are similar in character, and the effect of 1.5 Gy carbon-ion irradiation compares to that of 2.0-2.5 Gy X-irradiation.
TL;DR: The study showed the existence of a susceptibility locus for radiation lymphomagenesis on chromosome 16 and revealed aspects of the genetics of lymphoma susceptibility.
Abstract: BALB/cHeA (BALB/c) mice are sensitive to radiation lymphomagenesis, while STS/A (STS) mice are resistant. We have selected a recombinant mouse, R1, with a STS-derived D16Mit165-D16Mit34 segment in the vicinity of the centromere of chromosome 16 among progeny from a (CcS-7/Dem x BALB/c)F1 x BALB/c backcross. To test the susceptibility to radiation lymphomagenesis, we generated a genetic cross by mating the male and female R1 progeny obtained by 4-6 backcrosses of R1 to BALB/c. The mice were subjected to 4 x 1.7 Gy of X-irradiation. Of 120 mice analyzed, 94 developed lymphomas (91, of thymic type; 3, of nonthymic type) within 315 days of observation. The analysis indicated a link between the susceptibility to lymphomagenesis and the marker D16Mit34 on chromosome 16. The mice heterozygous for the BALB/c and STS alleles at D16Mit34 were less sensitive to lymphomagenesis than the mice homozygous at this locus. There was no significant difference in latency among the genotypes. Our study showed the existence of a susceptibility locus for radiation lymphomagenesis on chromosome 16 and revealed aspects of the genetics of lymphoma susceptibility.
Journal Article•
TL;DR: The results suggest that low-dose-induced tolerance to radiation may be dependent on a brief exposure to ozone, and a reduction in core temperature may be necessary to obtain tolerance effects in response to a mid-lethal dose of radiation.