Y Matsumoto, T Fujiwara, Y Honjo, N Sasaoka, T Tsuchida, S Nagao
{"title":"[人和大鼠胶质瘤DNA拓扑异构酶I活性的定量分析:对抗拓扑异构酶化学物喜树碱-11的表征和耐药机制]。","authors":"Y Matsumoto, T Fujiwara, Y Honjo, N Sasaoka, T Tsuchida, S Nagao","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Camptothecin-11 (CPT-11) is a new derivation of camptothecin, a plant alkaloid antitumor agent. Previous studies indicated that antitumor activity of CPT-11 was mediated through interaction of the drugs with its target enzyme, DNA topoisomerase I (topo I). In this study, we studied the relation between sensitivity to CPT-11 and topo I activity of glioma cells. Furthermore, we established CPT-11 resistant cell lines in order to elucidate potential mechanisms of drug resistance. A clear correlation between the sensitivities to CPT-11 and topo I activities in surgical glioma specimens was demonstrated. Activities of topo I in CPT-11 sensitive group (IC50 values for CPT-11; < 50 micrograms/ml) tended to be higher than those in CPT-11 resistant group (IC50 values; > or = 50). Topo I activity may serve as a novel marker to predict the sensitivity of gliomas to topo inhibitors. CPT-11 resistance cell lines (T98G/CPT-11 and C6) respectively exhibit a 5.4- and 7.3-fold increase in resistance to CPT-11. No differences in topo I activity and intracellular accumulation of CPT-11 were observed between parent and CPT-11 resistant lines. On the other hand, topo I from T98G/CPT-11 and C6/CPT-11 cells were at least 4- and 2-fold resistant to the inhibitory effect of the CPT-11 on the relaxation activity of topo I in comparison with their parent lines. This enzymological difference may be responsible for the resistance to CPT-11.</p>","PeriodicalId":79360,"journal":{"name":"Noshuyo byori = Brain tumor pathology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Quantitative analysis of DNA topoisomerase I activity in human and rat glioma: characterization and mechanism of resistance to antitopoisomerase chemical, camptothecin-11].\",\"authors\":\"Y Matsumoto, T Fujiwara, Y Honjo, N Sasaoka, T Tsuchida, S Nagao\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Camptothecin-11 (CPT-11) is a new derivation of camptothecin, a plant alkaloid antitumor agent. Previous studies indicated that antitumor activity of CPT-11 was mediated through interaction of the drugs with its target enzyme, DNA topoisomerase I (topo I). In this study, we studied the relation between sensitivity to CPT-11 and topo I activity of glioma cells. Furthermore, we established CPT-11 resistant cell lines in order to elucidate potential mechanisms of drug resistance. A clear correlation between the sensitivities to CPT-11 and topo I activities in surgical glioma specimens was demonstrated. Activities of topo I in CPT-11 sensitive group (IC50 values for CPT-11; < 50 micrograms/ml) tended to be higher than those in CPT-11 resistant group (IC50 values; > or = 50). Topo I activity may serve as a novel marker to predict the sensitivity of gliomas to topo inhibitors. CPT-11 resistance cell lines (T98G/CPT-11 and C6) respectively exhibit a 5.4- and 7.3-fold increase in resistance to CPT-11. No differences in topo I activity and intracellular accumulation of CPT-11 were observed between parent and CPT-11 resistant lines. On the other hand, topo I from T98G/CPT-11 and C6/CPT-11 cells were at least 4- and 2-fold resistant to the inhibitory effect of the CPT-11 on the relaxation activity of topo I in comparison with their parent lines. This enzymological difference may be responsible for the resistance to CPT-11.</p>\",\"PeriodicalId\":79360,\"journal\":{\"name\":\"Noshuyo byori = Brain tumor pathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1994-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Noshuyo byori = Brain tumor pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Noshuyo byori = Brain tumor pathology","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
[Quantitative analysis of DNA topoisomerase I activity in human and rat glioma: characterization and mechanism of resistance to antitopoisomerase chemical, camptothecin-11].
Camptothecin-11 (CPT-11) is a new derivation of camptothecin, a plant alkaloid antitumor agent. Previous studies indicated that antitumor activity of CPT-11 was mediated through interaction of the drugs with its target enzyme, DNA topoisomerase I (topo I). In this study, we studied the relation between sensitivity to CPT-11 and topo I activity of glioma cells. Furthermore, we established CPT-11 resistant cell lines in order to elucidate potential mechanisms of drug resistance. A clear correlation between the sensitivities to CPT-11 and topo I activities in surgical glioma specimens was demonstrated. Activities of topo I in CPT-11 sensitive group (IC50 values for CPT-11; < 50 micrograms/ml) tended to be higher than those in CPT-11 resistant group (IC50 values; > or = 50). Topo I activity may serve as a novel marker to predict the sensitivity of gliomas to topo inhibitors. CPT-11 resistance cell lines (T98G/CPT-11 and C6) respectively exhibit a 5.4- and 7.3-fold increase in resistance to CPT-11. No differences in topo I activity and intracellular accumulation of CPT-11 were observed between parent and CPT-11 resistant lines. On the other hand, topo I from T98G/CPT-11 and C6/CPT-11 cells were at least 4- and 2-fold resistant to the inhibitory effect of the CPT-11 on the relaxation activity of topo I in comparison with their parent lines. This enzymological difference may be responsible for the resistance to CPT-11.