• Bulletin of the Korean Chemical Society
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• 제30권10호
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• pp.2309-2317
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• 2009

Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though $N^7$-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.

• Journal of Preventive Medicine and Public Health
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• 제26권2호
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• pp.251-267
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• 1993

연폭로의 정도와 자각증상과의 관계를 알아보기 위하여 435명의 연폭로 남자 근로자와 212명의 일반 사무직 남자 근로자를 대상으로 연폭로 지표가 되는 혈중 연, 혈중 Zinc Protoporphyrin(ZPP), 요중 Delta-aminolevulinic acid(DALA), 혈색소, 혈구 용적 측정을 위한 혈액 시료 및 소변 시료를 채취하여 분석하였고, 연관련 자각증상 조사는 14개의 증상 조사 항목을(표 3 및 별첨 1) 피검자가 응답 하도록하여 상담 의사의 면접을 통한 확인을 거쳐 수집 하였다. 수집된 각 항목은 인체 조직계 증상군별로 1) 위장관계 증상 2) 신경과 근육 및 관절계 증상 3) 일반 체질적 증상 4) 정신과적 증상으로 구분하여 연폭로 지표 수준과 연폭로 작업 여부에 따른 자각증상 호소율을 비교 조사하여 얻은 결론은 다음과 같다. 1. 연폭로군에서 대조군보다 유의하게 높은 자각증상 호소율을 보인 증상군은 신경과 근육 및 관절계 증상으로 "손이나 발이 저리거나 쥐가 잘난다", "관절이 아프거나 쑤신다", "손가락, 손, 발 등에 힘이 없다", "근육통을 느낀다" 순 이었다. 2. 연폭로군과 대조군의 자각증상 호소율에 가장 큰 차이를 보인 증상 항목은 "손이나 발이 저리거나 쥐가 잘 난다"였으며, 전체 조사 대상에서 가장 높은 증상 호소율을 보인 증상 항목은 일반 체질적 자각 증상군의 "전보다 피곤감을 느낀다"였다. 3. 전체 조사 대상의 혈중 연과 혈중 ZPP 수준에 따른 연폭로량의 증가와 자각증상 호소율의 증가를 보인 증상 항목은 신경과 근육 및 관절계 증상군의 "손이나 발이 저리거나 쥐가 잘난다", "관절이 아프거나 쑤신다", "손가락. 손 발 등에 힘이 없다", "근육통을 느낀다"와 위장관계 증상군의 "아랫배가 아파서 고생한 적이 있다"였다. 4 연폭로군에서 혈중 연과 혈중 ZPP 수준에 따른 연폭로량의 증가와 자각증상 호소율의 증가를 보인 증상 항목은 신경과 근육 및 관절계 증상으로 혈중 연의 증가에 따라 증상 호소율이 증가하였다. 5. 연폭로군에서 39세 이하 와 40세 이상 연령군으로 나누어 비교시 39세 이하 군의 증상 호소율이 40세 이상 군보다 높게 나왔으며. 신경과 근육 및 관절계 증상이 39세이하 군에서 혈중 연의 증가와 함께, 40세 이상 군에서 혈중 ZPP의 증가와 함께 자각증상 호소율의 증가를 나타냈다. 6. 연폭로 지표에 따른 폭로수준과 증상 호소율과의 관계를 알아보기 위하여 대조군에 대한 폭로군, 연폭로군의 저농도 폭로군에 대한 고농도 폭로군의 교차비를 산출한 결과 신경과 근육 및 관절계 증상군의 "손이나 발이 저리거나 쥐가 잘난다", "관절이 아프거나 쑤신다", "손가락, 손, 발 등에 힘이 없다", "근육통을 느낀다"와 위장관계 증상군의 "아랫배가 아파서 고생한 적이 있다"가 연폭로량의 증가에 따른 교차비의 증가를 보여 양-반응의 관계를 추정할 수 있었다.

• 한국환경과학회지
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• 제26권3호
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• pp.345-362
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• 2017

The primary purpose of this study was to determine the risk of various disease outcomes due to exposure to cyanobacteria toxin (microcystin-LR) through drinking water in a Korean watershed. In order to determine the risk in a more quantitative way, the risk assessment framework developed by the National Research Council (NRC) of the United States (US) - hazard identification, dose-response relationship, exposure assessment, and risk characterization - was used in this study. For dose-response relationships, a computer software (BenchMark Dose Software (BMDS)) developed by the US Environmental Protection Agency (EPA) was used to fit the data from previous studies showing the relationship between the concentration of microcystin-LR and various disease outcomes into various dose-response models. For exposure assessment, the concentrations of microcystin-LR in the source water and finished water in a Korean watershed obtained from a recent study conducted by the Ministry of Environment of Korea were used. Finally, the risk of various disease outcomes due to exposure to cyanobacteria toxin (microcystin-LR) through drinking water was characterized by Monte-Carlo simulation using Crystall Ball program (Oracle Inc.) for adults and children. The results of this study suggest that the risk of disease due to microcystin-LR toxin through drinking water is very low and it appears that current water treatment practice should be able to protect the public from the harmful effects of cyanobacteria toxin (microcystin-LR) through drinking water.

• Journal of Preventive Medicine and Public Health
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• 제21권2호
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• pp.295-306
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• 1988

Dose-response relationship among blood cadmium concentrations, catalase and superoxide dismutase activities were studied with acutely intoxicated rats by cadmium. The Sprague-Dawley male rats to which single dose of $1{\sim}32mg/kg\;CdCl_2$ were administered into peritoneal cavity were sacrificed by decapitation at $3{\sim}36$ hours after the administration. Cadmium concentrations in blood increased significantly with dose of $CdCl_2$ administered and reached peak level at 3 hours later. Catalase activities in rats' testes were not correlated with esposure time elapsed after the administration in rats to which $1{\sim}2mg/kg\;of\;CdCl_2$ were administered, but they showed linear relationship with time in groups to which $4{\sim}32mg/kg\;of\;CdCl_2$ were administered. Cu, Zn-SOD activities in testes of acutely intoxicated rats by cadmium were not altered either by dosage or by time elapsed after the administration. Mn-SOD activities in the testes were also not influenced by dosage of $1{\sim}2mg/kg\;CdCl_2$, but remarkably inactivated by dosage of $4{\sim}32mg/kg\;CdCl_2$ with time elapsed after the administration. Neither catalase, Cu, Zn-SOD nor Mn-SOD activities of testes were correlated with blood cadmium concentrations in acutely intoxicated rats by cadmium.

• 응용통계연구
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• 제25권4호
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• pp.633-640
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• 2012

Biological methods are described for the assay of certain substances and preparations whose potency cannot be adequately assured by chemical or physical analysis. The principle applied through these assays is of a comparison with a standard preparation to determine how much of the examined substance produces the same biological effects as a given quantity (the Unit) of the standard preparation. In these dilution assays, to estimate the relative potencies of the unknown preparations to the standard preparations, it is necessary to compare dose-response relationships of standard and unknown preparations. The dose-response relationship in the dilution assay is non-linear and sigmoid when a wide range of doses is applied. The parallel line model (applied to the dose region with the steepest slope) is used to estimate the relative potency. In this paper, the statistical theory in the parallel line model is explained with an application to a dilution assay data. The parallel line method is implemented in a SAS program and is available at the author's homepage(http://cafe.daum.net/go.analysis).

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• 지역사회간호학회지
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• 제26권2호
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• pp.169-177
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• 2015

Purpose: Previous studies focused on the negative effects of Internet use such as obesity, depression, and addiction. However, few studies investigated whether the Internet use for an appropriate time has positive effects on adolescents' health. Thus, the purpose of the study was to examine the dose-response relationship between Internet use for non-academic purposes (NAP) and happiness/stress in adolescents. Methods: This study used data from the 2013 Korea Youth Risk Behavior Web-Based Survey. A total of 72,435 adolescents were included. Rao-Scott ${\chi}^2$ and multiple logistic regression were conducted. To test the dose-response relationship, this study examined how happiness/stress changed with increase in the time of Internet use for NAP. Results: After controlling for general characteristics, the odds ratios for being unhappy and stressful were lowest in adolescents using the Internet for NAP for more than 0 hour and less than an hour a day. Interestingly, students who did not use the Internet for NAP had a significantly higher risk of being unhappy/stressful than those using for more than 0 hour and less than an hour a day. Conclusion: Internet use for NAP for more than 0 hour and less than an hour a day has positive effects on happiness/stress in adolescents.

• 한국의학물리학회지:의학물리
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• 제33권4호
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• pp.158-163
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• 2022

Purpose: We subjected scanning electron microscopic (SEM) images of the active layer of EBT3 film to texture analysis to determine the dose-response curve. Methods: Uncoated Gafchromic EBT3 films were prepared for direct surface SEM scanning. Absorbed doses of 0-20 Gy were delivered to the film's surface using a 6 MV TrueBeam STx photon beam. The film's surface was scanned using a SEM under 100× and 3,000× magnification. Four textural features (Homogeneity, Correlation, Contrast, and Energy) were calculated based on the gray level co-occurrence matrix (GLCM) using the SEM images corresponding to each dose. We used R-square to evaluate the linear relationship between delivered doses and textural features of the film's surface. Results: Correlation resulted in higher linearity and dose-response curve sensitivity than Homogeneity, Contrast, or Energy. The R-square value was 0.964 for correlation using 3,000× magnified SEM images with 9-pixel offsets. Dose verification was used to determine the difference between the prescribed and measured doses for 0, 5, 10, 15, and 20 Gy as 0.09, 1.96, -2.29, 0.17, and 0.08 Gy, respectively. Conclusions: Texture analysis can be used to accurately convert microscopic structural changes to the EBT3 film's surface into absorbed doses. Our proposed method is feasible and may improve the accuracy of film dosimetry used to protect patients from excess radiation exposure.

• 한국환경보건학회지
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• 제43권4호
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• pp.247-256
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• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.153-157
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• 2016

Background: In radiation therapy, estimation of surface doses is clinically important. This study aimed to obtain an analytical relationship to determine the skin surface dose, kerma and the depth of maximum dose, with energies of 6 and 18 megavoltage (MV). Materials and Methods: To obtain the dose on the surface of skin, using the relationship between dose and kerma and solving differential equations governing the two quantities, a general relationship of dose changes relative to the depth was obtained. By dosimetry all the standard square fields of $5cm{\times}5cm$ to $40cm{\times}40cm$, an equation similar to response to differential equations of the dose and kerma were fitted on the measurements for any field size and energy. Applying two conditions: a) equality of the area under dose distribution and kerma changes in versus depth in 6 and 18 MV, b) equality of the kerma and dose at $x=d_{max}$ and using these results, coefficients of the obtained analytical relationship were determined. By putting the depth of zero in the relation, amount of PDD and kerma on the surface of the skin, could be obtained. Results: Using the MATLAB software, an exponential binomial function with R-Square >0.9953 was determined for any field size and depth in two energy modes 6 and 18MV, the surface PDD and kerma was obtained and both of them increase due to the increase of the field, but they reduce due to increased energy and from the obtained relation, depth of maximum dose can be determined. Conclusions: Using this analytical formula, one can find the skin surface dose, kerma and thickness of the buildup region.