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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.
김종춘(Jong-Choon Kim),신진영(Jin-Young Shin),신동호(Dong-Ho Shin),김성호(Sung-Ho Kim),이성배(Sung-Bae Lee),한정희(Jung-Hee Han),정용현(Yong-Hyun Chung),김현영(Hyeon-Yeung Kim),박승춘(Seung-Chun Park) 한국독성학회 2004 Toxicological Research Vol.20 No.3
The present study was carried out to investigate the potential toxicity of dimethyl disulfide<br/> by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation<br/> to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the<br/> end of treatment period, all males and females were sacrificed. During the test period, clinical signs,<br/> mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were<br/> examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher<br/> dose groups were significantly lower than those of the control group, respectively. The mean food<br/> consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared<br/> with the controls. Some treatment-related serum biochemical changes, including decreased alkaline<br/> phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300<br/> ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent<br/> manner, but these findings were considered to be of no toxicological significance. There were no<br/> adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group.<br/> Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation<br/> resulted in suppressed body weight gain and decreased food consumption at the dose of male<br/> 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose<br/> of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect<br/> level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day<br/> for female rats.
방사선의 발생독성 검색을 위한 단기 최기형성 시험법의 확립
김종춘(Jong-Choon Kim),김성호(Sung-Ho Kim),신동호(Dong-Ho Shin),신진영(Jin-Young Shin),김세라(Se-Ra Kim),이해준(Hae-June Lee),박승춘(Seung-Chun Park),조성기(Sung-Kee Jo),이윤실(Yun-Sil Lee) 한국독성학회 2004 Toxicological Research Vol.20 No.2
The present study was carried out to establish a short-term teratogenicity study for detecting developmental toxic potential induced by gamma radiation in ICR mice. Pregnant mice were exposed at dose levels of 0, 0.5, 1, 2, or 4 Gy on gestational day 8.5. All dams were subjected to caesarean section on gestational day 10.5 and their embryos were examined for growth, differentiation, and morphological abnormalities. An increase in the number of resorption was found at 4 Gy in a dose-dependent manner. Dose-dependent decreases in the developmental score of yolk sac<br/> circulation and olfactory system at above 1 Gy, in the number of somite pairs and developmental score of allantois, optic system, and maxillary process at above 2 Gy, and in the all growth and developmental parameters examined at 4 Gy were found. Various types of morphological abnormalities were seen at dose levels of 0.5 Gy or greater. Characteristic malformations induced by gamma radiation were abnormal axial rotation, hematoma, craniofacial hypoplasia, open neuropore, shortened prosencephalon, kinked somites, irregular somites, swelling, hydropericardium, absent branchial bar, and absent limb bud. Morphological alterations such as hematoma, craniofacial hypoplasia, open neuropore, and kinked somites were noted even in the lowest dose (0.5 Gy). These results indicated that the shortterm teratogenicity study established in this study can be a useful tool for not only detecting the developmental toxic potential induced by gamma radiation, but also screening radio-protective agents in ICR mice.
랫드에서 fluoroquinolone 항균제 DW-116 의 단회 경구투여에 의한 태반통과와 약물동태연구
김종춘(Jong Chun Kim),윤효인(Hyo In Yun),신호철(Ho Chul Shin),허정두(Jeong Du Hur),이종화(Jong Hwa Lee),정문구(Moon Koo Chung) 한국응용약물학회 2002 Biomolecules & Therapeutics(구 응용약물학회지) Vol.10 No.1
N/A The present study was conducted to investigate the placental transfer and pharmacokinetics of the fluoroquinolone antibacterial DW-116 in pregnant rats. The placental transfer and pharmacokinetics of DW-116 were examined after a single oral dose of 500 ㎎ [^14C]DW-116/㎏ on gestational day 18. Maternal and fetal tissues were collected at 0.17.0.5, 1, 2, 4, 8, and 24 h after dosing. Maximum radioactivity was detected in maternal plasma, placenta, and whole fetus at 1 h, and in amniotic plasma at 4 h after dosing. Thereafter, radioactivity gradually disappeared from these tissues and was 16∼28% of maximum levels at 24 h after dosing. Radioactivity in whole fetus were higher than those in the maternal plasma and placenta. The T_(1/2,abs), T_(1/2,β), AUC, T_max, and C_max in the maternal plasma were approximately 6 min, 13.3 h, 1620 ug^*hr/ml, 0.5 h, and 136 ug/ml, respectively. Those in the placenta were approximately 20 min, 12.3 h, 2150 ug^*h/ml, 1.0 h, and 172 ug/ml, respectively. Those in the whole fetus were 13 min, 12.8 h, 2549 ug^*h/ml, 1 h, and 191 ug/ml, respectively. In the amniotic fluid of maternal uterus, the T_(1/2,abs), T_(1/2,β), AUC, T_max, and C_max were approximately 1.3 h, 9.3 h, 2508 ug^*h/ml, 4.4 h, and 135 ug/ml, respectively. While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid. In conclusion, this study demonstrated that the absorption and distribution of DW- 116 in maternal plasma and placenta were extensively rapid, and that the test chemical well passed the blood-placenta barrier and was transferred to the fetus.
김종춘(Jong-Choon Kim),신진영(Jin-Young Shin),신동호(Dong-Ho Shin),김성호(Sung-Ho Kim),배춘식(Chun-Sik Bae),박승춘(Seung-Chun Park),차신우(Shin-Woo Cha),강부현(Boo-Hyon Kang),정문구(Moon-Koo Chung) 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.1
The present study was performed 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 ㎎/㎏/day of 2-BP or its vehicle (com oil) 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 histopathologic examinations. The early histopathological changes observed in testes and epididymides included degeneration and decrease of spermatogonia in stages Ⅰ~Ⅵ, degeneration and decrease of spermatocytes and multinuclear giant cells in stages Ⅶ~Ⅹ, mature spermatid retention in stages Ⅸ~Ⅺ, vacuolization of Sertoli cells, and degeneration of spermatogenic cells in epididymal ducts. On day 14 after treatment, a significant decrease in the weights of testes and seminal vesicles was found. Atrophy of seminiferous tubules, exfoliation of spermatogenic cells, degeneration and decrease of spermatogonia, degeneration and decrease of spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, oligozoospermia, and degeneration of spermatogenic cells in epididymal ducts were also observed. In addition, a slight non-significant decrease in testicular sperm head counts, daily sperm production 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 detecting the testicular toxic potential of new drug candidates in rats.
방사선의 발생독성 검색을 위한 단기 최기형성 시험법의 확립
김종춘(Jong-Choon Kim),김성호(Sung-Ho Kim),신동호(Dong-Ho Shin),신진영(Jin-Young Shin),김세라(Se-Ra Kim),이해준(Hae-June Lee),박승춘(Seung-Chun Park),조성기(Sung-Kee Jo),이윤실(Yun-Sil Lee) 한국독성학회 2004 Toxicological Research Vol.20 No.1
The present study was carried out to establish a short-term teratogenicity study for detecting developmental toxic potential induced by gamma radiation in ICR mice. Pregnant mice were exposed at dose levels of 0, 0.5, 1, 2, or 4 Gy on gestational day 8.5. All dams were subjected to caesarean section on gestational day 10.5 and their embryos were examined for growth, differentiation, and morphological abnormalities. An increase in the number of resorption was found at 4 Gy in a dose-dependent manner. Dose-dependent decreases in the developmental score of yolk sac circulation and olfactory system at above 1 Gy, in the number of somite pairs and developmental score of allantois, optic system, and maxillary process at above 2 Gy, and in the all growth and developmental parameters examined at 4 Gy were found. Various types of morphological abnormalities were seen at dose levels of 0.5 Gy or greater. Characteristic malformations induced by gamma radiation were abnormal axial rotation, hematoma, craniofacial hypoplasia, open neuropore, shortened prosencephalon, kinked somites, irregular somites, swelling, hydropericardium, absent branchial bar, and absent limb bud. Morphological alterations such as hematoma, craniofacial hypoplasia, open neuropore, and kinked somites were noted even in the lowest dose (0.5 Gy). These results indicated that the shortterm teratogenicity study established in this study can be a useful tool for not only detecting the developmental toxic potential induced by gamma radiation, but also screening radio-protective agents in ICR mice.
새만금 방조제 내측과 외측 조하대 대형저서동물의 생태학적 연구
김종춘 ( Jong Chun Kim ),마채우 ( Che Woo Ma ),복영욱 ( Young Wook Bok ) 한국환경생태학회 2014 한국환경생태학회지 Vol.28 No.4
본 연구는 새만금 지역에 서식하는 조하대 대형저서동물의 계절별 종조성과 양적 변화를 조사하여 저서동물의 주요 종 분포와 군집 변화양상을 파악하기 위하여 실시하였다. 전체 종수는 총 64종이었으며, 분류군별로는 환형동물 (Annelida)이 34종 출현하여 전체의 53.0%를 점유 하였으며, 절지동물(Arthropoda)과 연체동물(Mollusca)이 각각 12종 출현하여 18.8%을 차지하였으며, 기타동물(Other)이 6종으로 9.4%를 점유하였다. 개체수는 총 24,885개체로 단위 면적당 개체수는 4147.5개체/㎡였으며, 이중 환형동물이 19,805개체로 79.6%를 나타냈고, 연체동물이 4,620개체 로 18.5%, 기타 295개체 1.19%, 절지동물 165개체 0.7%를 차지하였다. Bray-Curtis 유사도(Similarity)를 분석한 결과, 새만금방조제를 기준으로 내측과 외측의 2개 그룹(A, B)으로 구분되어 나누어졌다. 또한, nMDS분석 결과와도 일치하는 것으로 나타났다. 저서오염지수(BPI)를 이용한 저서동물의 군집 분석결과, 각 정점별 지리적 위치, 내측 및 외측에 있어 뚜렷한 차이는 없는 것으로 나타났으나, 계절별로는 3월에 가장 양호한 것으로 조사되었다. This study was carried out to measure the seasonal changes in community structure and species composition of marobenthos on the subtidal area of Saemangeum regions. The macrobenthos comprised 64 species were during this study, predominately annelids (53.0%), arthropods (18.8%), mollusks (18.8%) and 9.4% were from other species. Total abundance was 24,885 individuals, comprising 19,805 individuals of annelids (79.6%), 4,620 individuals of mollusks (18.5%), 295 individuals of other species (1.2%), and 165 individuals of arthropods (0.7%). After analyzing the bray-curtis similarity, had two large groups (A, B) the inside and outside of Saemangeum dike. They all matched the nMDS analysis. I evaluated the benthic community health using BPI (Benthic pollution Index). There are no significant differences between the station position and the inside or outside of Saemangeum dike. But, highest BPI level was in March.
Biological responses in rats exposed to the Hebei Spirit oil spill constituents
Jung Ah Kim(김정아),Sung-Ho Kim(김성호),Miyoung Yang(양미영),Changjong Moon(문창종),Jong-Choon Kim(김종춘),Chun-Sik Bae(배춘식),Jong-Sik Jang(장종식),Su Ryeon Noh(노수련),Gwi Heum Eom(엄귀흠),Hyun Sook Bae(배현숙),Eun Kyoung Yang( 환경독성보건학회 2013 한국독성학회 심포지움 및 학술발표회 Vol.2013 No.10