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Title   백서 간암유발과정중 DNA Topoisomerases 와 암유전자 c-myc 의 발현에 관한 연구 ( Studies on Expression of DNA Topoisomerases Genes and Protooncogene c- Myc during Hepatocarcinogenesis )
Publicationinfo   1993 Jan; 025(05): 636-651.
Key_word   DNA topoisomerases, 3-methyl dimethylaminoazobenzene, c-myc
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Abstract   We have investigated interrelationship between histological changes and the expression of DNA topoisamerases(Topo I and II) and proto-oncogenes, c-myc during the course of hepatocarcinogenesis induced by 3-methyl dimethylaminoazobenzene. 1) Oval cell praliferation and vacuolated changes, liver cirrhosis, cholangiocarcinoma or hepatocellular carcinoma were observed in the 2nd, 8th, 12th weeks, respectively during hepatocarcinogenesis. 2) Specific activity of Topo I from normal liver was 203 unit/mg protein/min and that of Topo II was absent. The activity of Topo I and II was increased in the 2nd week during hepatocarcinogenesis, and the maximal increment of them occured in the 4th week. In case of Topo I activity, maximal incrernent was 2.6 folds, in comparison with that of normal liver. After 8 weeks the enzyme activity was gradually decreased. Topo II was sharply decreased and then disaPpeared after 10 weeks. 3) The level of Topo I mRNA was increased in the 4th week and showed maximal increment in the 6th week. After 8 weeks the transcript was decreased significantly, and then maintained as normsl leveL 4) Protein level of Topo I of heyatoma was higher than normal liver. 5) The level of c-myc mRNA was highly increased in the 4th week, respectively. 6) ATP, GTP inhibited the activity of Topo I from normal and cancer tissue of rat liver in the presence of Mg, K, while in the absence of them, the activity was activated. 7) ddATP and ddGTP inhibited the activity of Topo I, while ddCTP and ddTTP activated. 8) Camptothecin and 10-OH-camptothecin inhibited the enzymes of normal and cancer tissue, and ID50 was 20 uM and 5 uM, respectively. 9) Etoposide and adriamycin inhibited Topo II, and the ID50 was 25 uM and 6.25 uM, respectively. These results suggest that c-myc and DNA topoisomerase I may play a important role during hepatocarcinogenesis induced by 3-MeDAB, and the possible induction of differentiation of oval cells by DNA topoisomerases inhibitors was discussed.
저 자   황병두(Byung Doo Hwang),원상희(Sang Hee Won),권기량(Gi Ryang Kweon),김계영(Kye Young Kim),강대영(Dae Young Kang),곽상태(Sang Tae Kwak),임규(Kyu Lim)