• Journal of Radiation Industry
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• v.7 no.2_3
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• pp.109-113
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• 2013

In a previous study, a relatively high dose of gamma radiation (1 kGy) did not fully induce typical SOS genes such as sulA, recA, recN, and din in Salmonella Typhimurium (S. Typhimurium) (Lim et al. 2008, Gene expression profiles following high-dose exposure to gamma radiation in Salmonella enterica serovar Typhimuium. J. Radiat. Ind. 3:111-119). In this study, we examined changes in the transcriptional repertoire of S. Typhimurium after a dose of 10 Gy using DNA microarrays. It was found that more than half (~65%) of the 26 up-regulated genes belong to the SOS regulon: ten genes are typical SOS genes, and seven genes are Salmonella prophage genes, which are known to be activated by LexA cleavage. Among 29 down-regulated genes, the function of five genes with the most decreased expression is associated with carbohydrate transport and energy production. This suggests that upon exposure to gamma radiation cells may cease growing by reducing the metabolic activity, and repair DNA damage using a DNA repair system such as the SOS response system. The difference in expression of the SOS genes between a high (1 kGy) and low (10 Gy) dose of radiation shows the possibility that cells may opt for one of multiple regulatory circuits in response to the specific gamma radiation dose.

• Journal of Photoscience
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• v.9 no.2
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• pp.197-200
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• 2002

UVR-induced immunosuppression contributes to skin cancer. The aim was to construct accurate dose response curves for primary and secondary contact sensitivity for solar-simulated UVR (ssUVR; 290-400nm), UVA and UVB as the role of UVA in immunosuppression is controversial. We used a xenon arc source. The mice were immobilised, enabling accurate dosing. C57BL/6 mice were immunosuppressed at half the dose of ssUVR required to cause sunburn but not by higher doses (up to the sunburn dose). Thus, ssUVR causes systemic immunosuppression only over a narrow, low dose range. UVA caused suppression at low but not high doses whereas UVB induced immunosuppression at all doses tested. 8 weeks later the mice were resensitised to assess tolerance. Mice exposed to the minimum immunosuppressive dose of ssUVR prior to primary sensitisation were tolerant to re-sensitisation. However, at higher doses of ssUVR, these mice were protected from tolerance. Interestingly, while low doses of UV A caused immunosuppression, even lower doses enhanced the response to the second sensitisation. Higher doses of UVA had no affect. UVB induced tolerance in a dose related manner. Thus, ssUVR only induces immunosuppression and tolerance over a narrow dose range. Both UVA and UVB are immunosuppressive at this dose, while higher doses of UVA protect from the suppressive effects of UVB. Surprisingly very low doses of UVA enhanced memory development. Thus UVR has complex effects on the immune system depending on dose and spectrum.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.211-218
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• 2003

Background: Vitamin C is an essential nutrient, taken as a daily supplement by many people. Recently, high-dose vitamin C is considered as a therapeutic regimen in some clinical situations. Until now, few studies have been done with the effects of high-dose vitamin C on the immune response. Methods: In this experiment, the effects of high-dose vitamin C on cell-mediated immune response in immunologically competent mice were evaluated. After intraperitoneal injection of 2.5, 5, or 10 mg/day of vitamin C for 10 days, delayed type hypersensitivity (DTH) was provoked against DNFB in the pinnae as a model for cell-mediated immune response. Severity of DTH reaction was evaluated as the thickness of pinnae, and the vitamin C levels were measured in the serum, liver, kidney, lung, pinnae, and splenocytes. Results: After challenge, the thickness increased at its peak on the $2^{nd}$ day in all groups. On the first day, the pinnae were thicker in the injected groups than in the control. On the contrary, the increment of the pinnae thickness was attenuated and the number of cells infiltrated in the site of DTH decreased proportionately to the amount of vitamin C administered from the second day on. With vitamin C exogenously given, the serum level peaked at 30 min after injection, and returned abruptly to its basal level without accumulation. However, it accumulated in the liver, kidney, and especially in the pinnae inflamed and splenopcytes, proportionately to the amount administered. Conclusion: Based on these results, it is suggested that, in one hand, exogenously administered high-dose vitamin C accumulated in the splenocytes and presumably changed the function of them resulting in the augmented cell-mediated immune response, as was revealed in the first day of DTH reaction. On the other hand, it seems likely that the vitamin C also showed anti-inflammatory effects.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.22 no.3
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• pp.175-183
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• 2012

Objectives: This study developed a harmonized method for risk assessment based on the Hazard & Risk Evaluation of Chemicals (HREC) according to the Industrial Safety and Health Act (ISHA). Methods: Three preliminary studies, performed during 2010 and 2011 by the Occupational Safety and Health Research Institute and three academic research groups, were compared. The differences in risk assessment, especially in the dose-response assessment method, were analyzed. A new harmonized method for dose-response assessment was suggested and its applicability for the HREC was examined. Results: Considering the various steps of each dose-response assessment, the equivalent steps in quantitative correction, uncertainty factor 2 (UF2) for intra-species uncertainty, and UF3 for the experimental period in the uncertainty correction were relatively high. Using our new method, the total correction values (quantitative correction plus uncertainty correction) ranged from 72~15,789 to 30~60, and the ratio of the threshold limit value (TLV) to the reference concentration decreased from 12.8~1900 to 5.4~11.8. Furthermore, when we performed risk characterization by our new method, hazard quotient (HQ) values for chloroethylene, epichlorohydrin, and barium sulfate became 3.0, 14.1, and 1.13 respectively, whereas three previous studies reported HQ values of 7.1, 4580, and 87.3 considering reasonable maximum exposure (RME) conditions. HQs of the three chemicals were calculated to be 0.6, 2.4, and 0.1 respectively, when compared to their TLVs. Conclusions: Our new method could be applicable for the HREC because the total correction values and the ratio of TLVs were within reasonable ranges. It is also recommended that additional risk management measures be applied for epichlorohydrin, for which the HQ values were greater than 1 when compared with both reference values and the TLV. Our proposed method could be used to harmonize dose-response assessment methods for the implementation of risk assessment based on the HREC according to ISHA.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.118-126
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• 2001

Purpose : In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. Materials and Methods : From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was $48.2{\pm}7.9\;Gy$ in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at $4\~8$ weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. Results : An objective response was observed in 106 of 158 patients, giving a response rate of $67.1\%$. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only $29.2\%$ showed objective response in patients treated with dose less than 40 Gy, while $68.6\%\;and\;77.1\%$ showed major response in patients with $40\~50\;Gy$ and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Conclusion : Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.1.1-1.13
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• 2016

Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (A-bomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down's syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.

• Journal of the Korean Data and Information Science Society
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• v.25 no.5
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• pp.987-998
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• 2014

The primary purpose of this paper is to derive a benchmark dose lower limit (BMDL) of lead for the attention deficit/hyperactive disorder (ADHD) based on a longitudinal cohort data set which is referred to as CHEER data set. The CHEER data were recently recruited from the Ministry of Environment of S. Korea to investigate the effect of environment on children's health We first confirm the correlation of ADHD with the blood lead level using a linear mixed effect model. We report from the longitudinal characteristic of CHEER data that ADHD scores tend to have "regression to the mean". A dose-response curve of blood lead level with ADHD being the end point is derived and from this dose-response curve a few BMDLs are derived based on corresponding assumptions on the benchmark region.

• Radiation Oncology Journal
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• v.4 no.2
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• pp.89-97
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• 1986

Using as assay for jejunal crypt stem cell survival, dose-response curves for the reproductive capacity of crypt stem cells of mouse jejunum exposed to multifractionated gamma-ray irradiation (single, 2, 3, 4, 5, 8, 10, 12, and 16 fractions) were analyzed and single-dose survival curve of these cells was constructed. The following conclusion were drawn: 1) Survival curves for higher numbers of dose fractions were displaced to higher dose, and characterized by increasingly shallower slopes. 2) The single-dose survival curve had broad shoulder, Dq=460 cGy, remaining near-exponential over initial dose range 0 to 300 cGy, with initial slope 1Do=474 cGy. 3) At fractionated dose En the range of 180 to 450 cGy, the average recovered dose per fraction interval was approximately $50\%$ of the dose per fraction. 4) The value of $\alpha/\beta$ ratio by using of linear regression analysis for the reciprocal dose plots was 8.3 Gy which lied in the range of 6-14 Gy for early-reacting tissues. 5) The linear-quadratic model for dose-response formula offers valid approximations for at 1 doses to be used in radiotherapy, only two parameters to be determined, and considerable convenience in practical applications.

• Journal of Microbiology and Biotechnology
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• v.11 no.3
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• pp.524-528
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• 2001

The measurement of radiation response using simple and informative techniques would be of great value in studying the genetic risk following occupational, therapeutic, or accidental exposure to radiation. When patients receive radiation therapy, many suffer from side effects. Since each patient receives a different dose due to different physical conditions, it is important to measure the exact dose of radiation received by each patient to lessen the side effects. Even though several biological dosimetric systems have already been developed, there is no ideal system that can satisfy all the criteria for an idean dosimetric system, especially for low-dose radiation as used in radiation therapy. In this study, an SOS Chromotest of E. coli PQ37 was evaluated as a novel dosimeter for low-dose gamma-rays. E. coli PQ37 was originally developed to screen chemical mutagens using the SOS Chromotest-a colorimtric assay, based on the induction of ${\beta}$-galactosidase ue to DNA damage. The survival fraction of E. coli PQ37 decreased dose-dependently with an increasing dose of cobalt-60 gamma-rays. Also, a good linear correlation was found between the biological damage revealed by the ${\beta}$-galactosidase expression and the doses of gamma-rays. The expression of ${\beta}$-galactosidase activity that responded to low-dose radiation under 1 Gy was $Y=0.404+(0.089{\pm}0.3)D+(-0.018{\pm}0.16)D^2$ (Y, absorbance at 420 nm; D, Dose of irradiation) as calculated using Graph Pad In Plot and Excel. When a rabbit was fed with capsules containing an agar block embdded with E. coli PQ37 showed a linear response to the radiation doses. Accordingly, the results confirm that E. coli PQ37 can be used as a sensitive biological dosimeter fro cobalt-60 gamma-rays. To the best of our knowledge, this is the first time that a bacterium has been used as a biological dosimeter, especially for low-dose radiation.

• Radiation Oncology Journal
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• v.38 no.1
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• pp.35-43
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• 2020

Purpose: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). Materials and Methods: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. Results: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. Conclusion: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.