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손우찬(Woo-Chan Son) 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.2
It is vital to understand background data such as normal phisiology, anatomy, biochemical events and background pathology in the use of laboratory animals. As minipig is rarely used laboratory species, the basic background data are scarce. In order to establish a general profile of histopathologic background data in 1-year old Göttingen minipigs, data from 32 minipigs were collected, and characteristic histologic features were tabulated and described. The most common findings were a minimal degree of inflammatory cell infiltrate found in the kidney, lungs, gastrointestinal tract, or adrenal glands; followed by mineralisation seen in the lungs, thymus, salivary glands, kidney or pituitary. Arteritis/periarteritis found in the kidney and stomach were morphologically similar to idiopathic canine polyarteritis in Beagle dogs. Testicular degeneration of tubular germinal epithelium, mostly found bilaterally, was seen in 12 out of 16 minipigs. There were many other findings but generally minimal grade and occur in other laboratory animal species. The aim of this report is to provide minipig users with a useful reference guide to aid sound understandings.
손우찬(Woo-Chan Son),김배환(Bae-Hwan Kim),장동덕(Dong-Deuk Jang),한범석(Beom-Seok Han),김종춘(Jong-Choon Kim),이제봉(Je-Bong Lee),신진섭(Jin-Sup Shin),김형진(Hyoung-Chin Kim) 한국농약과학회 2004 농약과학회지 Vol.8 No.4
It has been debating about conducting and interpretating of 2-year rodent carcinogenicity bioassay. Although some criticisms arising in usefulness, it has been still known that long-term carcinogenicity studies using rodents would be the only assay system to predict any possible human risks, which would not be replaced. Both regulatory agencies and academies have developed some assay models, however, there have been controversy whether those study designs and interpretations are based on sound scientific rationale and validated data. Such kinds of issues including choice of species/strain, dose level selection, duration of study, number of animals per group, historical control data, monitoring parameters, terminal investigations, peer review, statistics, alternative assay models, interpretation of neoplastic lesions, and risk assessments, were reviewed.
독성병리 Peer Review의 중요성과 실제적 접근방법
손우찬(Woo-Chan Son),김배환(Bae-Hwan Kim),장동덕(Dong-Deuk Jang),한범석(Beom-Seok Han),양기화(Ki-Hwa Yang),이영순(Yong-Soon Lee) 한국독성학회 2004 Toxicological Research Vol.20 No.1
Evaluation of toxicological pathology is to some extend subjective judgments by pathologist and the accuracy of pathologist’s works is based on the individual training and experiences. It has been required to establish a peer review system for toxicologic pathology and these review system has been employed by various practice of toxicological pathology. It would be pointed out that the possible causes of drifts in pathology are due to 1) lack of knowledge or experience of individual pathologists, 2) poorly maintained consistence of grading among animals in study, 3) different interpretation of findings between pathologists, or 4) pathology data processing. Example cases of diagnostic errors and current practice of peer review including tissue selection criteria, documentation and problem resolution for short-term and carcinogenicity studies were introduced. For sound regulatory<br/> system and high integrity of practice in toxicological pathology, current approaches of peer review system were reviewed.
손우찬(Woo-Chan Son),김배환(Bae-Hwan Kim),장동덕(Dong-Deuk Jang),김철규(Chull-Kyu Kim),한범석(Beom-Seok Han),김종춘(Jong-Choon Kim),강부현(Boo-Hyon Kang),이제봉(Je-Bong Lee),최양규(Yang-Kyu Choi),김형진(Hyoung-Chin Kim) 한국독성학회 2005 Toxicological Research Vol.21 No.1
Transgenic mouse models have been introduced and accepted by regulatory bodies as an alternative to carcinogenicity assay models to predict and evaluate chemical carcinogens. The recent research outcomes in transgenic mouse models have made progressive advances in the understanding of chemical carcinogenesis and the evaluation of potential human carcinogens. However, these models still remain to be insufficient assay systems although the insufficiencies have been recognised and are being resolved. Based on up to date information from literature, this review article intends to understand currently accepted transgenic mouse models, issues arising from study design, interpretation of the study, results of validation project and their cancer prediction rate, and further perspectives of cancer assay models from the regulatory view point.
정자생성 주기법을 이용한 고환독성 평가 필요성과 정량적인 고환독성 평가방법에 대한 고찰
손우찬(Woo-Chan Son),김종춘(Jong-Choon Kim),유일재(Il Je Yu) 한국독성학회 2003 Toxicological Research Vol.19 No.2
Since histopathological examination was known to be the most sensitive evaluation for testicular toxicity, regulatory authorities have been published the guidelines on practical testicular assay approach. Those guidelines specified details of evaluation including fixation, embedding, staining, histological examination and also seminiferous tubular staging methods. However, there have been confusing understanding among toxicologists and even pathologists on staging theory and its application on industrial testicular toxicity. Guidelines did not intend to conduct quantitative assay with staging but recommended the use of knowledge of staging. To count each tubular stage with statistical<br/> analysis is known to be time consuming and labor burdening work but the significance of toxicity has little value. It also has been pointed out that the application of staging theory for longer-term toxicity considered to be lacking of rationale. It could be recommended that qualitative assay with awareness of germ cell loss is more efficient method rather than quantitative counting of each tubular stage. Therefore it would be required that comprehensive understanding of testicular toxicity evaluation and the use of testicular staging method.
랫드에서 고환독성의 정색을 위한 정량적 평가법의 확립: 2-bromopropane의 예
차신우,배주현,손우찬,신진영,신동호,김성호,박승춘,김종춘,Cha Shin-Woo,Bae Joo-Hyun,Son Woo-Chan,Shin Jin-Young,Shin Dong-Ho,Kim Sung-Ho,Park Seung-Chun,Kim Jong-Choon 한국생명과학회 2005 생명과학회지 Vol.15 No.3
The aims of the study were to establish a short-term screening test for detecting testicular toxicity of chemicals in rats and to determine whether a 2-week administration period is sufficient to detect testicular toxicity of 2-bromopropane (2-BP) as an example. Male Sprague-Dawley rats were subcutaneously administered with 1000 mg/kg/day of 2-BP or its vehicle for 2 weeks. Ten male rats each were sacrificed on days 3, 7 and 14 after the initiation of treatment. Parameters of testicular toxicity included genital organ weights, testicular sperm head counts, epididymal sperm counts, motility and morphology, and qualitative and quantitative histopathologic examinations. The early histopathological changes observed on day 3 of treatment included degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, and decreased number of spermatogonia in stages II and V. On day 7 of treatment, atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in stages VII and XII. On day 14 after treatment, a significant decrease in the weights of testes and seminal vesicles was found. Atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in all spermatogenic stages were also observed. In addition, a slight non-significant decrease in testicular sperm head counts, daily sperm production rate and epididymal sperm counts was found. The results showed that 2 weeks of treatment is sufficient to detect the adverse effects of 2-BP on male reproductive organs. It is considered that the short-term testicular toxicity study established in this study can be a useful tool for screening the testicular toxic potential of new drug candidates in rats.
Single dose toxicity study of CKD-602, a new camptothecin anticancer agent, in Beagle dogs
김종춘,신동호,박승춘,손우찬,차신우,한정희,배주현,서정은,정문구,Kim, Jong-Choon,Shin, Dong-Ho,Park, Seung-Chun,Son, Woo-Chan,Cha, Shin-Woo,Han, Junghee,Bae, Joo-Hyun,Suh, Jeong-Eun,Chung, Moon-Koo The Korean Society of Veterinary Science 2004 大韓獸醫學會誌 Vol.44 No.1
The present study was carried out to investigate the potential acute toxicity of CKD-602 by a single intravenous dose in Beagle dogs. The test chemical was administered intravenously to male and female Beagle dogs at dose levels of 0.3, 0.5, or 2.5 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. All males and females of the 2.5 mg/kg dose group were found dead between the fourth and seventh day after the injection. Treatment related clinical signs, including vomiting, anorexia, mucous stool, diarrhea, and no stool were observed. Decrease or suppression of body weight was observed in a dose-dependent manner. In autopsy, dark red discoloration of the gastrointestinal tract, atrophy of the thymus, paleness of the spleen, sporadic dark red spots of the lung and petechia of the heart were observed in dead animals of the 2.5 mg/kg dose group. There were no specific adverse effects on males and females of the 0.3 and 0.5 mg/kg dose groups, except for the transient clinical signs such as anorexia, vomiting, and mucus/no stool. On the basis of the results, it was concluded that a single intravenous injection of CKD-602 to Beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. The absolute toxic dose of this chemical was 2.5 mg/kg for both genders. The $LD_{50}$ value was 1.1 mg/kg (95% confidence limit not specified) for both genders. The no-observed-effect level (NOEL) was considered to be below 0.3 mg/kg for both genders.