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Toggle생태 독성 평가의 새로운 패러다임 번역에 대해서 알아 보겠습니다(한영번역)
생태 독성 평가의 새로운 패러다임 번역(한국어 원본)최근 생태 독성 평가 분야에서는 화학물질에 대한 독성 반응을 nominal concentration으로 제시되어진 초기노출 조건과의 단순 비교만으로는 온전한 용량 반응관계를 설명할 수 없음을 인지하고 이를 개선하기 위한 이론적, 방법적 패러다임의 변화들이 시도되고 있다. 실제적으로 독성물질들이 생체내에서 독성 반응을 나타내기 위해서는 우선적으로 test system안에서의 흡착, 증발과 같은 손실과정을 거치고 생물체내로 들어가야하며, target site of action에 도달하기 전 distribution과 biotransformation과 같은 toxicokinetic process를 거쳐야 한다. 이러한 과정은 노출 농도를 nominal concentration으로 표기하는 방식이 독성 반응을 설명하기에 현실성이 매우 결여되어진 방향이며, 생물학적 활용성(bioavailability)를 고려하지 않은 결과를 도출 할 수 있음을 보여주는 것이다. 이러한 문제들을 보완하기 위해 독성반응을 분석할 때 생체내 농도(internal concentration)또는 화학물질의 활성도(chemical activity)를 고려할 수 있는 새로운 방법들을 개발하기 시작하였다. 화학물질을 고분자 물질에 용해시킨 뒤, 이를 dosing phase로 제공하여 미디어 내에서 물질의 활성도를 일정하게 유지시키는 passive dosing방법이 이러한 대체 시험 방법으로 최근 생태독성 분야에 적용 되고 있다. 특히, 수용해도가 낮은 소수성 유해물질에 대한 수계 생물종의 노출 실험에 passive dosing method가 최근 가장 많이 적용되고 있다 Gene expression은 외부의 effector들을 감지한 receptor들의 DNA와의 수용체 결합으로 촉진되어진 messenger RNA가 대응을 위한 단백질 분자의 합성 정보를 전달하기 위한 과정을 detection하는 것이다. 이러한 gene expression biomarker는 protein 또는 enzyme 의 활성이 생체내에서 나타나기 이전의 단계를 확인할 수 있는 매우 민감한 endpoint이다. 이러한 까닭에 생물체 내의 독성 반응 활성에 관여하는 실제적인 독성 농도의 정의는 매우 중요하다고 할 수 있다. |
생태 독성 평가의 새로운 패러다임 번역(영어 번역본)In the field of ecotoxicological evaluation, it has been recently recognized that simple comparison of toxicological response to chemicals and initial exposure conditions presented as nominal concentration cannot accurately describe the dose-response relationship. To address this problem, various changes in the theoretical and methodological paradigm are being attempted. In order for toxins to elicit toxicological response in the body, they must enter the organism through processes such as adsorption and evaporation, which involves decrease in the toxin concentration, and they must undergo toxicokinetic processes such as biodistribution and biotransformation prior to reaching the target site of action. These processes show that using nominal concentration as the exposure concentration is an unrealistic representation of toxicological response and may not take into the bioavailability of the toxins. In order to address these issues, researchers have devised new methods to take into account the internal concentration or chemical activity of the toxins. One of such alternative methods is passive dosing, which involves solubilizing toxin in polymeric material and providing it as a dosing phase to maintain chemical activity of the toxin within the media at a constant level. This method is now being applied to the field of ecotoxicology, and is the most frequently employed method for exposure of aquatic organisms to hydrophobic hazardous substances with low water solubility. Gene expression biomarker detects the process by which the messenger RNA (mRNA), which is stimulated by the complex of DNAs with receptors that have detected external effectors, delivers information for synthesis of proteins for response to the effectors. Such biomarkers are highly sensitive end points that can be used to detect changes prior to protein or enzymatic activity in the organism. Due to this reason, the definition of actual toxin concentration involved in activation of toxicological response within the organism is very important. In this study, we compared the conventional spiking method using nominal concentration as the reference and the new passive dosing method that can main chemical activity at a constant level. As shown in Figure 1A, single exposure by spiking method resulted in rapid decline in freely dissolved toxin concentration, which is directly related to toxicological response, from the onset of the experiment. Especially, lower volume led to larger loss (Figure 1A) such that even if same number of organisms were exposed to the same nominal concentration, about 0.2 mg/L less chemical was delivered per hour to the organisms with smaller volume. Such difference is reflected by large difference in the expression pattern that varies with total exposure medium volume (Figure 2). From these results, it was concluded that it is hard to quantify dose-response relationship using the spiking method as variables such as exposure volume, biomass, and expression duration are difficult to control using this method. However, exposure at constant concentration using the passive dosing method resulted in maintenance of freely dissolved concentration for C. elegans, which was enabled by the CP distribution equilibrium between the PDMS and the medium to neutralize the effect of different total exposure volume or biomass. Also, gene expression increased linearly over time when C. elegans was exposed with the passive dosing method (Figure 3). This trend was continued to be observed in cyp35a2 and cyp35a3 genes even when the exposure concentration has been decreased (Figure 4); when exposure concentration was decreased from 0.3 mg/L of CP to 0.15 mg/L and 0.06 mg/L , slope of the positive trend for the two genes decreased by 35% and 65%, respectively. This result showed that under environment in which stable exposure is guaranteed, toxicological response of sensitive molecular-level biomarkers such as gene expression displayed concentration- and time-dependent dose-response relationship. The reference value of 0.3 mg/L of CP corresponds to one-tenth of EC50 to C elegans according to previous literature, but no changes in C. elegans were visually observed with the spiking method at that concentration [REF]. However, when passive dosing was used to maintain the free concentration at 0.3 mg/L, abnormal deformations of the body of C. elegans were observed after 10 hours of exposure. As provided in the Supporting Data, after 10 hours of exposure, its body started twisting in the alpha-shape in the middle, and the organism died after 24 hours with the body exploded in the alpha-shape. Along with linear increase of gene expression over time, this phenomenon can be explained by the increased residual amount of CP inside the body. In general, CP is eliminated through metabolism of cytochrome p450. However, passive dosing constantly provides CP at the pre-determined freely dissolved concentration level regardless of how much CP has been eliminated, which leads to continued increase of residual CP in the body. As a result, C. elegans must continue metabolism using cyp35a2 and cyp35a3, leading to increased gene expression over time. However, when exposure has been continued for over 10 hours as in this study, CP saturates the capability of C. elegans to store inside the body, eliciting higher-level effect of body deformation and ultimately the death of the organism. Gene expression is a very sensitive end point that is an excellent biomarker for evaluating and monitoring ecological environment. However, gene expression that responds sensitively to the early phase of exposure varied significantly with exposure environment such as the medium, exposure concentration, exposure duration, and biomass. Passive dosing method involved using PDMS to maintain the freely dissolved concentration of a substance within the medium, thereby allowing the definition of dose-response relationship between the amount of the substance with toxicity at an earlier time than that conventional spiking method. Results from our study suggests that the passive dosing method accounting for freely dissolved chemical concentration is a promising method for toxicological evaluation using sensitive biomarkers at the molecular level. |
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이상 국립독성연구원에서 의뢰한 생태 독성 평가의 새로운 패러다임 번역(한영번역)의 일부를 살펴 보았습니다.
번역은 기버 번역