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DNA Topoisomerase : the Mechanism of Resistance to DNA Topoisomerase II Inhibitor VP-16
https://hiroshima.repo.nii.ac.jp/records/2013243
https://hiroshima.repo.nii.ac.jp/records/201324309f13981-a1c2-45de-9394-393ee6352bf1
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
HiroshimaJMedSci_38_197.pdf (640.4 KB)
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| Item type | デフォルトアイテムタイプ_（フル）(1) | |||||||
|---|---|---|---|---|---|---|---|---|
| 公開日 | 2023-03-18 | |||||||
| タイトル | ||||||||
| タイトル | DNA Topoisomerase : the Mechanism of Resistance to DNA Topoisomerase II Inhibitor VP-16 | |||||||
| 言語 | en | |||||||
| 作成者 |
Hong, Jae Hoon
× Hong, Jae Hoon
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| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 主題 | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | DNA topoisomernse II | |||||||
| 主題 | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | VP-16 | |||||||
| 主題 | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | Drug resistance | |||||||
| 主題 | ||||||||
| 主題Scheme | NDC | |||||||
| 主題 | 490 | |||||||
| 内容記述 | ||||||||
| 内容記述 | K6-1 and 50B-3 cell lines, resistant to VP-16, a DNA topoisomerase II inhibitor, were established from two different types of cells respectively: human T-cell derived acute lymphoblastic leukemia cell line RPMI8402 and mouse mammary tumor cell line FM3A. IC50 values of K6-1 and 50B-3 cells to VP-I6, evaluated by the colony forming ability on methyl cellulose medium, were 11- and 84-fold higher than their sensitive parental cell lines, respectively. Membrane permeability of the drug was not responsible for the resistance in K6-l and 50B-3 cells. Quantitative analysis of drug-induced DNA cleavage (so called cleavable complex formation) was performed using 32P end-labeled pBR322 restriction fragments. The formation of the topoisomerase II-DNA cleavable complex stimulated by VP-16 in 50B-3 cells was approximately 1/5 compared with that of FM3A wild-type cells. Dot blot analysis of RNA extracted from these cell lines showed that the levels of mRNA for DNA topoisomerase II in 50B-3 cells were markedly decreased and that catalytic activity was reduced to 1/2-113 compared with that of parent cells. There was a slight reduction of DNA topoisomerase II mRNA in K6-1 cells. However, DNA topoisomerase II activities were similar in wild-type and K6-1 cells. In addition, 50B-3 cells showed cross resistance to VM-26, m-AMSA and adriamycin, whereas K6-1 cells exhibited increased resistance only to VM-26. These resistant cell lines did not show collateral sensitivity to CPT-11, a DNA topoisomerase I inhibitor. Southern blot analysis of genomic DNA did not show any change in the restriction pattern of the DNA topoisomerase II gene between the parental and their resistant lines. These findings suggest that the reduced levels in DNA topoisomerase II contribute to the drug resistance of 50B-3 cells. | |||||||
| 言語 | en | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | Earlier versions of this work were presented at the 47th Annual Meeting of the Japanese Cancer Association (1988, Tokyo) and at the 51th Annual Meeting of the Japanese Hematological Society (1989, Gunma). | |||||||
| 出版者 | ||||||||
| 出版者 | Hiroshima University Medical Press | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||
| 資源タイプ | departmental bulletin paper | |||||||
| 出版タイプ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| 関連情報 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 2561562 | |||||||
| 収録物識別子 | ||||||||
| 収録物識別子タイプ | ISSN | |||||||
| 収録物識別子 | 0018-2052 | |||||||
| 収録物識別子 | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AA00664312 | |||||||
| 開始ページ | ||||||||
| 開始ページ | 197 | |||||||
| 書誌情報 |
Hiroshima Journal of Medical Sciences Hiroshima Journal of Medical Sciences 巻 38, 号 4, p. 197-207, 発行日 1989-12 |
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| 旧ID | 38131 | |||||||
