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유전자수준에서 돌연변이 유발기전을 밝히는 Transgenic Mutagenesis Assay
류재천,윤지윤,조경혜,장일무,Ryu, Jae-Chun,Youn, Ji-Youn,Cho, Kyung-Hae,Chang, Il-Moo 한국환경성돌연변이발암원학회 1998 한국환경성돌연변이·발암원학회지 Vol.18 No.1
Transgenic animal and cell line models which are recently developed and used in toxicology fields combined with molecular biological technique, are powerful tools to study the mechanism of mutation in vivo and in vitro, respectively. Transgenic models, which have exogenous DNA incorporated into their genome, carry recoverable shuttle vector containing reporter genes to assess endogenous effects or alteration in specific genes related to disease processes. The lac I and lac Z gnee most widely used as a mutational target in transgenic systems. The assay is performed by treatment with putative mutagenic agents, isolation of genomic DNA from cells or tissues, exposure the isolated DNA to in vitro packaging extract, plating and sequencing. The results from these processes provide not only mutant frequency as quantitative evaluation but also mutational spectrum as qualitative evaluation of various agents. Therefore we introduce and review the principle, detailed procedure and application of transgenic mutagenesis assay system in toxicology fields especially in mutagenesis and carcinogenesis.
DK1002에 대한 급성독성시험 및 유전독성에 관한 연구
류재천,김경란,김현주,정상운,김명국,박희석,김용해,Ryu, Jae-Chun,Kim, Kyung-Ran,Kim, Hyun-Joo,Jung, Sang-Oun,Kim, Myung-Kuk,Park, Hee-Sock,Kim, Yong-Hae 한국독성학회 1998 Toxicological Research Vol.14 No.3
The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.