• Title/Summary/Keyword: Dose-response assessment

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Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

  • Saberi, Alihossein;Khodamoradi, Ehsan;Birgani, Mohammad Javad Tahmasebi;Makvandi, Manoochehr
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8553-8557
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    • 2016
  • Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

BIOLOGICALLY-BASED DOSE-RESPONSE MODEL FOR NEUROTOXICITY RISK ASSESSMENT

  • Slikker, William Jr.;Gaylor, David W.
    • Toxicological Research
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    • v.6 no.2
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    • pp.205-213
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    • 1990
  • The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

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Estimation of the Number of Salmonellosis Using Microbial Risk Assessment Methodology (미생물 위해성 평가 방법을 이용한 살모넬라 발생수 추정)

  • 최은영;박경진
    • The Korean Journal of Community Living Science
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    • v.15 no.2
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    • pp.167-177
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    • 2004
  • The number of foodborne salmonellosis was estimated by using microbial risk assessment(MRA) methodology and the possibility of application was studied through comparison with previous results. The contamination levels of Salmonella sp. were estimated by using published domestic studies(1997∼2000) and monitoring data (1999∼2001) from food-safety related institutes. Data on food consumption came from the 2001 National Health and Nutrition Survey, and dose-response models from studies in other countries. Simulation results showed that there were 753,368 cases of salmonellosis in Korea in 1 year, which is about 115 times that reported in previous years and lower than the WHO's estimation increase. From these results, microbial risk assessment is likely to be available for estimation of the number of foodborne illnesses and determination of the order of priority in food-safety management. Butthe verification methods are not established and most of the data on contamination levels of foodborne bacteria, food consumption, and dose-response relationships have not been established. In addition, the actual conditions of circulation, storage and cooking must be studied further.

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Dose-Response Relationship of Micronucleus Frequency in Pollen Mother Cells of Tradescantia (자주달개비 화분모세포 미세핵 생성률의 방사선량-반응 관계)

  • Kim, Jin-Kyu;Song, Hi-Sup;Hyun, Soung-Hee
    • Journal of Radiation Protection and Research
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    • v.24 no.4
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    • pp.225-230
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    • 1999
  • This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronuclei showed a good dose-response relationship in the range of dose $0{\sim}50$ cGy. On the basis of the relationship, a dose of 1 cGy results maximally in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiations. The micronucleus assay can be applied to biological risk assessment of environmental toxicants, and to integrity test of water or soils of interest.

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Risk Assessment of Escherichia coli Infection from Use of Interactive Waterscape Facilities (수경시설 물놀이에 따른 대장균 감염의 위해도 분석)

  • Zo, Young-Gun
    • Journal of Environmental Health Sciences
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    • v.38 no.1
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    • pp.73-81
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    • 2012
  • Objectives: With the goal of quantifying the risk of children contracting gastroenteritis while playing at interactive waterscape facilities and evaluating the adequacy of current water quality regulations, risk assessment was performed with Escherichia coli as pathogen. Methods: Abundances of E. coli in the waters of interactive water features in South Korea were acquired from survey reports. A gamma distribution describing the volume of water swallowed by children during swimming activities was adopted. Exposure rate and risk were calculated by Monte Carlo simulation and dose-response models for various pathogenic E. coli. Results: E. coli was detected in 25 out of 40 facilities, with range of ~1,600 CFU/100 ml. The abundance fitted an exponential distribution. Simulated exposures ranged ${\sim}1.9{\times}10^{10}$ CFU, varying greater along E. coli abundance than the volume of water. Risk of children being infected by enterohemorrhagic E. coli was high, with range of ~0.85. When E. coli abundance was <200 CFU/100 ml, which is the current government threshold, the risk decreased to <0.43. Although the guideline successfully reduced the risk of adults being infected by a less virulent E. coli strains (<0.03), the risk for children could not be quantified due to lack of dose-response models for those pathogens for children. Conclusions: Under the current guideline, children are at risk of being infected if water is contaminated with by enterohemorrhagic E. coli. For other E. coli strains, the risk appears to be considerably less. The result warrants need for developing dose-response models for children for each pathogenic E. coli strain.

Quantitative microbial risk assessment of Campylobacter jejuni in jerky in Korea

  • Ha, Jimyeong;Lee, Heeyoung;Kim, Sejeong;Lee, Jeeyeon;Lee, Soomin;Choi, Yukyung;Oh, Hyemin;Yoon, Yohan
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.2
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    • pp.274-281
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    • 2019
  • Objective: The objective of this study was to estimate the risk of Campylobacter jejuni (C. jejuni) infection from various jerky products in Korea. Methods: For the exposure assessment, the prevalence and predictive models of C. jejuni in the jerky and the temperature and time of the distribution and storage were investigated. In addition, the consumption amounts and frequencies of the products were also investigated. The data for C. jejuni for the prevalence, distribution temperature, distribution time, consumption amount, and consumption frequency were fitted with the @RISK fitting program to obtain appropriate probabilistic distributions. Subsequently, the dose-response models for Campylobacter were researched in the literature. Eventually, the distributions, predictive model, and dose-response model were used to make a simulation model with @RISK to estimate the risk of C. jejuni foodborne illness from the intake of jerky. Results: Among 275 jerky samples, there were no C. jejuni positive samples, and thus, the initial contamination level was statistically predicted with the RiskUniform distribution [RiskUniform (-2, 0.48)]. To describe the changes in the C. jejuni cell counts during distribution and storage, the developed predictive models with the Weibull model (primary model) and polynomial model (secondary model) were utilized. The appropriate probabilistic distribution was the BetaGeneral distribution, and it showed that the average jerky consumption was 51.83 g/d with a frequency of 0.61%. The developed simulation model from this data series and the dose-response model (Beta Poisson model) showed that the risk of C. jejuni foodborne illness per day per person from jerky consumption was $1.56{\times}10^{-12}$. Conclusion: This result suggests that the risk of C. jejuni in jerky could be considered low in Korea.

High and Low Dose Folinic Acid, 5-Fluorouracil Bolus and Continuous Infusion for Poor-Prognosis Patients with Advanced Colorectal Carcinoma

  • Bano, Nusrat;Najam, Rahila;Mateen, Ahmed;Qazi, Faaiza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3589-3593
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    • 2012
  • Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$), glucose 5%, 5-FU ($400mg/m^2$) and 22 hr. CIV ($600mg/m^2$) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$)for five days, 5FU($425mg/m^2$) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.

X-band EPR dosimetry using minimum mass of tooth enamel for use in radiological accidents

  • Jae Seok Kim;Byeong Ryong Park;Han Sung Kim;In Mo Eo;Jaeryong Yoo;Won Il Jang;Minsu Cho;HyoJin Kim;Yong Kyun Kim
    • Nuclear Engineering and Technology
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    • v.56 no.1
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    • pp.123-131
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    • 2024
  • Electron paramagnetic resonance (EPR) dosimetry for a tooth from an individual exposed is well known as retrospective dosimetry in radiological accidents. A major constraint of the conventional X-band tooth-EPR dosimetry is the necessity to extract the tooth of the exposed patient for dose assessment. In this study, to conduct the dose assessments of exposed patients through part-extraction of tooth enamel, the minimum detectable dose (MDD) of the tooth enamel was evaluated based on the amount of mass. Further, a field test was conducted via intercomparison using various dose assessment methods to verify the feasibility of X-band tooth-EPR dosimetry using the minimum mass of tooth enamel. The intercomparison results demonstrated that effective dose determination via X-band tooth-EPR dosimetry is reliable. Consequently, it was determined that the minimum mass of tooth enamel required to evaluate an absorbed dose above 0.5 Gy is 15 mg. Thus, EPR dosimetry using 15 mg of tooth enamel can be applied in the triage and initial medical response stages for patients exposed during radiological accidents. This approach represents an advancement in managing radiological accidents by offering a more efficient and less invasive method of dose assessment.