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. 1994 Apr;69(4):687–697. doi: 10.1038/bjc.1994.131

Altered stability of etoposide-induced topoisomerase II-DNA complexes in resistant human leukaemia K562 cells.

M K Ritke 1, D Roberts 1, W P Allan 1, J Raymond 1, V V Bergoltz 1, J C Yalowich 1
PMCID: PMC1968798  PMID: 8142256

Abstract

K562 leukaemia cells were selected for resistance using 0.5 microM etoposide (VP-16). Cloned K/VP.5 cells were 30-fold resistant to growth inhibition by VP-16 and 5- to 13-fold resistant to m-AMSA, adriamycin and mitoxantrone. K/VP.5 cells did not overexpress P-glycoprotein; VP-16 accumulation was similar to that in K562 cells. VP-16-induced DNA damage was reduced in cells and nuclei from K/VP.5 cells compared with K562 cells. Topoisomerase II protein was reduced 3- to 7-fold and topoisomerase II alpha and topoisomerase II beta mRNAs were each reduced 3-fold in resistant cells. After drug removal, VP-16-induced DNA damage disappeared 1.7 times more rapidly and VP-16-induced DNA-topoisomerase II adducts dissociated 1.5 times more rapidly in K/VP.5 cells than in K562 cells. ATP (1 mM) was more effective in enhancing VP-16-induced DNA damage in nuclei isolated from sensitive cells than in nuclei from resistant cells. In addition, ATP (0.3-5 mM) stimulated VP-16-induced DNA-topoisomerase II adducts to a greater extent in K562 nuclei than in K/VP.5 nuclei. Taken together, these results indicate that resistance to VP-16 in a K562 subline is associated with a quantitative reduction in topoisomerase II protein and, in addition, a distinct qualitative alteration in topoisomerase II affecting the stability of drug-induced DNA-topoisomerase II complexes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman P., Glover C. V., Osheroff N. Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro. Proc Natl Acad Sci U S A. 1985 May;82(10):3164–3168. doi: 10.1073/pnas.82.10.3164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ackerman P., Glover C. V., Osheroff N. Phosphorylation of DNA topoisomerase II in vivo and in total homogenates of Drosophila Kc cells. The role of casein kinase II. J Biol Chem. 1988 Sep 5;263(25):12653–12660. [PubMed] [Google Scholar]
  3. Beran M., Andersson B. S. Development and characterization of a human myelogenous leukemia cell line resistant to 4'-(9-acridinylamino)-3-methanesulfon-m-anisidide. Cancer Res. 1987 Apr 1;47(7):1897–1904. [PubMed] [Google Scholar]
  4. Bugg B. Y., Danks M. K., Beck W. T., Suttle D. P. Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7654–7658. doi: 10.1073/pnas.88.17.7654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cardenas M. E., Dang Q., Glover C. V., Gasser S. M. Casein kinase II phosphorylates the eukaryote-specific C-terminal domain of topoisomerase II in vivo. EMBO J. 1992 May;11(5):1785–1796. doi: 10.1002/j.1460-2075.1992.tb05230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chan V. T., Ng S. W., Eder J. P., Schnipper L. E. Molecular cloning and identification of a point mutation in the topoisomerase II cDNA from an etoposide-resistant Chinese hamster ovary cell line. J Biol Chem. 1993 Jan 25;268(3):2160–2165. [PubMed] [Google Scholar]
  7. Charcosset J. Y., Saucier J. M., Jacquemin-Sablon A. Reduced DNA topoisomerase II activity and drug-stimulated DNA cleavage in 9-hydroxyellipticine resistant cells. Biochem Pharmacol. 1988 Jun 1;37(11):2145–2149. doi: 10.1016/0006-2952(88)90573-4. [DOI] [PubMed] [Google Scholar]
  8. Chen G. L., Yang L., Rowe T. C., Halligan B. D., Tewey K. M., Liu L. F. Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Nov 10;259(21):13560–13566. [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Chung T. D., Drake F. H., Tan K. B., Per S. R., Crooke S. T., Mirabelli C. K. Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9431–9435. doi: 10.1073/pnas.86.23.9431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cleveland D. W., Yen T. J. Multiple determinants of eukaryotic mRNA stability. New Biol. 1989 Nov;1(2):121–126. [PubMed] [Google Scholar]
  12. Cole S. P., Chanda E. R., Dicke F. P., Gerlach J. H., Mirski S. E. Non-P-glycoprotein-mediated multidrug resistance in a small cell lung cancer cell line: evidence for decreased susceptibility to drug-induced DNA damage and reduced levels of topoisomerase II. Cancer Res. 1991 Jul 1;51(13):3345–3352. [PubMed] [Google Scholar]
  13. Corbett A. H., Fernald A. W., Osheroff N. Protein kinase C modulates the catalytic activity of topoisomerase II by enhancing the rate of ATP hydrolysis: evidence for a common mechanism of regulation by phosphorylation. Biochemistry. 1993 Mar 2;32(8):2090–2097. doi: 10.1021/bi00059a029. [DOI] [PubMed] [Google Scholar]
  14. Danks M. K., Schmidt C. A., Cirtain M. C., Suttle D. P., Beck W. T. Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26. Biochemistry. 1988 Nov 29;27(24):8861–8869. doi: 10.1021/bi00424a026. [DOI] [PubMed] [Google Scholar]
  15. Danks M. K., Schmidt C. A., Deneka D. A., Beck W. T. Increased ATP requirement for activity of and complex formation by DNA topoisomerase II from human leukemic CCRF-CEM cells selected for resistance to teniposide. Cancer Commun. 1989;1(2):101–109. doi: 10.3727/095535489820875309. [DOI] [PubMed] [Google Scholar]
  16. Danks M. K., Warmoth M. R., Friche E., Granzen B., Bugg B. Y., Harker W. G., Zwelling L. A., Futscher B. W., Suttle D. P., Beck W. T. Single-strand conformational polymorphism analysis of the M(r) 170,000 isozyme of DNA topoisomerase II in human tumor cells. Cancer Res. 1993 Mar 15;53(6):1373–1379. [PubMed] [Google Scholar]
  17. Danks M. K., Yalowich J. C., Beck W. T. Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26). Cancer Res. 1987 Mar 1;47(5):1297–1301. [PubMed] [Google Scholar]
  18. Davies S. M., Robson C. N., Davies S. L., Hickson I. D. Nuclear topoisomerase II levels correlate with the sensitivity of mammalian cells to intercalating agents and epipodophyllotoxins. J Biol Chem. 1988 Nov 25;263(33):17724–17729. [PubMed] [Google Scholar]
  19. DeVore R. F., Corbett A. H., Osheroff N. Phosphorylation of topoisomerase II by casein kinase II and protein kinase C: effects on enzyme-mediated DNA cleavage/religation and sensitivity to the antineoplastic drugs etoposide and 4'-(9-acridinylamino)methane-sulfon-m-anisidide. Cancer Res. 1992 Apr 15;52(8):2156–2161. [PubMed] [Google Scholar]
  20. Deffie A. M., Batra J. K., Goldenberg G. J. Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines. Cancer Res. 1989 Jan 1;49(1):58–62. [PubMed] [Google Scholar]
  21. Drake F. H., Hofmann G. A., Bartus H. F., Mattern M. R., Crooke S. T., Mirabelli C. K. Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II. Biochemistry. 1989 Oct 3;28(20):8154–8160. doi: 10.1021/bi00446a029. [DOI] [PubMed] [Google Scholar]
  22. Drake F. H., Zimmerman J. P., McCabe F. L., Bartus H. F., Per S. R., Sullivan D. M., Ross W. E., Mattern M. R., Johnson R. K., Crooke S. T. Purification of topoisomerase II from amsacrine-resistant P388 leukemia cells. Evidence for two forms of the enzyme. J Biol Chem. 1987 Dec 5;262(34):16739–16747. [PubMed] [Google Scholar]
  23. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  24. Ferguson P. J., Fisher M. H., Stephenson J., Li D. H., Zhou B. S., Cheng Y. C. Combined modalities of resistance in etoposide-resistant human KB cell lines. Cancer Res. 1988 Nov 1;48(21):5956–5964. [PubMed] [Google Scholar]
  25. Fernandes D. J., Danks M. K., Beck W. T. Decreased nuclear matrix DNA topoisomerase II in human leukemia cells resistant to VM-26 and m-AMSA. Biochemistry. 1990 May 1;29(17):4235–4241. doi: 10.1021/bi00469a028. [DOI] [PubMed] [Google Scholar]
  26. Filipski J., Kohn K. W. Ellipticine-induced protein-associated DNA breaks in isolated L1210 nuclei. Biochim Biophys Acta. 1982 Sep 27;698(3):280–286. doi: 10.1016/0167-4781(82)90158-0. [DOI] [PubMed] [Google Scholar]
  27. Friche E., Danks M. K., Schmidt C. A., Beck W. T. Decreased DNA topoisomerase II in daunorubicin-resistant Ehrlich ascites tumor cells. Cancer Res. 1991 Aug 15;51(16):4213–4218. [PubMed] [Google Scholar]
  28. Glisson B. S., Smallwood S. E., Ross W. E. Characterization of VP-16-induced DNA damage in isolated nuclei from L1210 cells. Biochim Biophys Acta. 1984 Oct 5;783(1):74–79. doi: 10.1016/0167-4781(84)90080-0. [DOI] [PubMed] [Google Scholar]
  29. Glisson B., Gupta R., Smallwood-Kentro S., Ross W. Characterization of acquired epipodophyllotoxin resistance in a Chinese hamster ovary cell line: loss of drug-stimulated DNA cleavage activity. Cancer Res. 1986 Apr;46(4 Pt 2):1934–1938. [PubMed] [Google Scholar]
  30. Gupta R. S. Genetic, biochemical, and cross-resistance studies with mutants of Chinese hamster ovary cells resistant to the anticancer drugs, VM-26 and VP16-213. Cancer Res. 1983 Apr;43(4):1568–1574. [PubMed] [Google Scholar]
  31. Harker W. G., Slade D. L., Dalton W. S., Meltzer P. S., Trent J. M. Multidrug resistance in mitoxantrone-selected HL-60 leukemia cells in the absence of P-glycoprotein overexpression. Cancer Res. 1989 Aug 15;49(16):4542–4549. [PubMed] [Google Scholar]
  32. Harker W. G., Slade D. L., Drake F. H., Parr R. L. Mitoxantrone resistance in HL-60 leukemia cells: reduced nuclear topoisomerase II catalytic activity and drug-induced DNA cleavage in association with reduced expression of the topoisomerase II beta isoform. Biochemistry. 1991 Oct 15;30(41):9953–9961. doi: 10.1021/bi00105a020. [DOI] [PubMed] [Google Scholar]
  33. Heck M. M., Hittelman W. N., Earnshaw W. C. In vivo phosphorylation of the 170-kDa form of eukaryotic DNA topoisomerase II. Cell cycle analysis. J Biol Chem. 1989 Sep 15;264(26):15161–15164. [PubMed] [Google Scholar]
  34. Hinds M., Deisseroth K., Mayes J., Altschuler E., Jansen R., Ledley F. D., Zwelling L. A. Identification of a point mutation in the topoisomerase II gene from a human leukemia cell line containing an amsacrine-resistant form of topoisomerase II. Cancer Res. 1991 Sep 1;51(17):4729–4731. [PubMed] [Google Scholar]
  35. Kamath N., Grabowski D., Ford J., Kerrigan D., Pommier Y., Ganapathi R. Overexpression of P-glycoprotein and alterations in topoisomerase II in P388 mouse leukemia cells selected in vivo for resistance to mitoxantrone. Biochem Pharmacol. 1992 Sep 1;44(5):937–945. doi: 10.1016/0006-2952(92)90126-4. [DOI] [PubMed] [Google Scholar]
  36. Kohn K. W., Erickson L. C., Ewig R. A., Friedman C. A. Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry. 1976 Oct 19;15(21):4629–4637. doi: 10.1021/bi00666a013. [DOI] [PubMed] [Google Scholar]
  37. Kroll D. J., Rowe T. C. Phosphorylation of DNA topoisomerase II in a human tumor cell line. J Biol Chem. 1991 Apr 25;266(12):7957–7961. [PubMed] [Google Scholar]
  38. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  39. Lee M. S., Wang J. C., Beran M. Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II. J Mol Biol. 1992 Feb 20;223(4):837–843. doi: 10.1016/0022-2836(92)90245-f. [DOI] [PubMed] [Google Scholar]
  40. Liu L. F. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 1989;58:351–375. doi: 10.1146/annurev.bi.58.070189.002031. [DOI] [PubMed] [Google Scholar]
  41. Long B. H., Wang L., Lorico A., Wang R. C., Brattain M. G., Casazza A. M. Mechanisms of resistance to etoposide and teniposide in acquired resistant human colon and lung carcinoma cell lines. Cancer Res. 1991 Oct 1;51(19):5275–5283. [PubMed] [Google Scholar]
  42. Matsuo K., Kohno K., Takano H., Sato S., Kiue A., Kuwano M. Reduction of drug accumulation and DNA topoisomerase II activity in acquired teniposide-resistant human cancer KB cell lines. Cancer Res. 1990 Sep 15;50(18):5819–5824. [PubMed] [Google Scholar]
  43. Minford J., Pommier Y., Filipski J., Kohn K. W., Kerrigan D., Mattern M., Michaels S., Schwartz R., Zwelling L. A. Isolation of intercalator-dependent protein-linked DNA strand cleavage activity from cell nuclei and identification as topoisomerase II. Biochemistry. 1986 Jan 14;25(1):9–16. doi: 10.1021/bi00349a002. [DOI] [PubMed] [Google Scholar]
  44. Mirski S. E., Evans C. D., Almquist K. C., Slovak M. L., Cole S. P. Altered topoisomerase II alpha in a drug-resistant small cell lung cancer cell line selected in VP-16. Cancer Res. 1993 Oct 15;53(20):4866–4873. [PubMed] [Google Scholar]
  45. Nelson E. M., Tewey K. M., Liu L. F. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361–1365. doi: 10.1073/pnas.81.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Norman M. R., Thompson E. B. Characterization of a glucocorticoid-sensitive human lymphoid cell line. Cancer Res. 1977 Oct;37(10):3785–3791. [PubMed] [Google Scholar]
  47. Odaimi M., Andersson B. S., McCredie K. B., Beran M. Drug sensitivity and cross-resistance of the 4'-(9-acridinylamino)methanesulfon-m-anisidide-resistant subline of HL-60 human leukemia. Cancer Res. 1986 Jul;46(7):3330–3333. [PubMed] [Google Scholar]
  48. Osheroff N. Biochemical basis for the interactions of type I and type II topoisomerases with DNA. Pharmacol Ther. 1989;41(1-2):223–241. doi: 10.1016/0163-7258(89)90108-3. [DOI] [PubMed] [Google Scholar]
  49. Patel S., Fisher L. M. Novel selection and genetic characterisation of an etoposide-resistant human leukaemic CCRF-CEM cell line. Br J Cancer. 1993 Mar;67(3):456–463. doi: 10.1038/bjc.1993.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Per S. R., Mattern M. R., Mirabelli C. K., Drake F. H., Johnson R. K., Crooke S. T. Characterization of a subline of P388 leukemia resistant to amsacrine: evidence of altered topoisomerase II function. Mol Pharmacol. 1987 Jul;32(1):17–25. [PubMed] [Google Scholar]
  51. Politi P. M., Arnold S. T., Felsted R. L., Sinha B. K. P-glycoprotein-independent mechanism of resistance to VP-16 in multidrug-resistant tumor cell lines: pharmacokinetic and photoaffinity labeling studies. Mol Pharmacol. 1990 Jun;37(6):790–796. [PubMed] [Google Scholar]
  52. Pommier Y., Kerrigan D., Schwartz R. E., Swack J. A., McCurdy A. Altered DNA topoisomerase II activity in Chinese hamster cells resistant to topoisomerase II inhibitors. Cancer Res. 1986 Jun;46(6):3075–3081. [PubMed] [Google Scholar]
  53. Pommier Y., Schwartz R. E., Kohn K. W., Zwelling L. A. Formation and rejoining of deoxyribonucleic acid double-strand breaks induced in isolated cell nuclei by antineoplastic intercalating agents. Biochemistry. 1984 Jul 3;23(14):3194–3201. doi: 10.1021/bi00309a013. [DOI] [PubMed] [Google Scholar]
  54. Ritke M. K., Yalowich J. C. Altered gene expression in human leukemia K562 cells selected for resistance to etoposide. Biochem Pharmacol. 1993 Dec 3;46(11):2007–2020. doi: 10.1016/0006-2952(93)90643-b. [DOI] [PubMed] [Google Scholar]
  55. Roberts D. W., Foglesong P. D., Parganas E., Wiggins L. Reduced formation of lesions in the DNA of a multidrug-resistant L1210 subline selected for teniposide resistance. Cancer Chemother Pharmacol. 1989;23(3):161–168. doi: 10.1007/BF00267948. [DOI] [PubMed] [Google Scholar]
  56. Ross W. E., Glaubiger D., Kohn K. W. Qualitative and quantitative aspects of intercalator-induced DNA strand breaks. Biochim Biophys Acta. 1979 Mar 28;562(1):41–50. doi: 10.1016/0005-2787(79)90124-2. [DOI] [PubMed] [Google Scholar]
  57. Sahai B. M., Kaplan J. G. A quantitative decatenation assay for type II topoisomerases. Anal Biochem. 1986 Aug 1;156(2):364–379. doi: 10.1016/0003-2697(86)90267-8. [DOI] [PubMed] [Google Scholar]
  58. Sahyoun N., Wolf M., Besterman J., Hsieh T., Sander M., LeVine H., 3rd, Chang K. J., Cuatrecasas P. Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1603–1607. doi: 10.1073/pnas.83.6.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Saijo M., Enomoto T., Hanaoka F., Ui M. Purification and characterization of type II DNA topoisomerase from mouse FM3A cells: phosphorylation of topoisomerase II and modification of its activity. Biochemistry. 1990 Jan 16;29(2):583–590. doi: 10.1021/bi00454a036. [DOI] [PubMed] [Google Scholar]
  60. Saijo M., Ui M., Enomoto T. Growth state and cell cycle dependent phosphorylation of DNA topoisomerase II in Swiss 3T3 cells. Biochemistry. 1992 Jan 21;31(2):359–363. doi: 10.1021/bi00117a007. [DOI] [PubMed] [Google Scholar]
  61. Sinkule J. A., Evans W. E. High-performance liquid chromatographic analysis of the semisynthetic epipodophyllotoxins teniposide and etoposide using electrochemical detection. J Pharm Sci. 1984 Feb;73(2):164–168. doi: 10.1002/jps.2600730207. [DOI] [PubMed] [Google Scholar]
  62. Sugawara I., Iwahashi T., Okamoto K., Sugimoto Y., Ekimoto H., Tsuruo T., Ikeuchi T., Mori S. Characterization of an etoposide-resistant human K562 cell line, K/eto. Jpn J Cancer Res. 1991 Sep;82(9):1035–1043. doi: 10.1111/j.1349-7006.1991.tb01940.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sullivan D. M., Eskildsen L. A., Groom K. R., Webb C. D., Latham M. D., Martin A. W., Wellhausen S. R., Kroeger P. E., Rowe T. C. Topoisomerase II activity involved in cleaving DNA into topological domains is altered in a multiple drug-resistant Chinese hamster ovary cell line. Mol Pharmacol. 1993 Feb;43(2):207–216. [PubMed] [Google Scholar]
  64. Sullivan D. M., Latham M. D., Rowe T. C., Ross W. E. Purification and characterization of an altered topoisomerase II from a drug-resistant Chinese hamster ovary cell line. Biochemistry. 1989 Jun 27;28(13):5680–5687. doi: 10.1021/bi00439a051. [DOI] [PubMed] [Google Scholar]
  65. Takano H., Kohno K., Ono M., Uchida Y., Kuwano M. Increased phosphorylation of DNA topoisomerase II in etoposide-resistant mutants of human cancer KB cells. Cancer Res. 1991 Aug 1;51(15):3951–3957. [PubMed] [Google Scholar]
  66. Tewey K. M., Chen G. L., Nelson E. M., Liu L. F. Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Jul 25;259(14):9182–9187. [PubMed] [Google Scholar]
  67. Tewey K. M., Rowe T. C., Yang L., Halligan B. D., Liu L. F. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984 Oct 26;226(4673):466–468. doi: 10.1126/science.6093249. [DOI] [PubMed] [Google Scholar]
  68. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Tsai-Pflugfelder M., Liu L. F., Liu A. A., Tewey K. M., Whang-Peng J., Knutsen T., Huebner K., Croce C. M., Wang J. C. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177–7181. doi: 10.1073/pnas.85.19.7177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  71. Webb C. D., Latham M. D., Lock R. B., Sullivan D. M. Attenuated topoisomerase II content directly correlates with a low level of drug resistance in a Chinese hamster ovary cell line. Cancer Res. 1991 Dec 15;51(24):6543–6549. [PubMed] [Google Scholar]
  72. Webb C. F., Eneff K. L., Drake F. H. A topoisomerase II-like protein is part of an inducible DNA-binding protein complex that binds 5' of an immunoglobulin promoter. Nucleic Acids Res. 1993 Sep 11;21(18):4363–4368. doi: 10.1093/nar/21.18.4363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Woessner R. D., Mattern M. R., Mirabelli C. K., Johnson R. K., Drake F. H. Proliferation- and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell Growth Differ. 1991 Apr;2(4):209–214. [PubMed] [Google Scholar]
  74. Yalowich J. C. Effects of microtubule inhibitors on etoposide accumulation and DNA damage in human K562 cells in vitro. Cancer Res. 1987 Feb 15;47(4):1010–1015. [PubMed] [Google Scholar]
  75. Yalowich J. C., Goldman I. D. Analysis of the inhibitory effects of VP-16-213 (etoposide) and podophyllotoxin on thymidine transport and metabolism in Ehrlich ascites tumor cells in vitro. Cancer Res. 1984 Mar;44(3):984–989. [PubMed] [Google Scholar]
  76. Zhang H., D'Arpa P., Liu L. F. A model for tumor cell killing by topoisomerase poisons. Cancer Cells. 1990 Jan;2(1):23–27. [PubMed] [Google Scholar]
  77. Zwelling L. A. DNA topoisomerase II as a target of antineoplastic drug therapy. Cancer Metastasis Rev. 1985;4(4):263–276. doi: 10.1007/BF00048092. [DOI] [PubMed] [Google Scholar]
  78. Zwelling L. A., Hinds M., Chan D., Mayes J., Sie K. L., Parker E., Silberman L., Radcliffe A., Beran M., Blick M. Characterization of an amsacrine-resistant line of human leukemia cells. Evidence for a drug-resistant form of topoisomerase II. J Biol Chem. 1989 Oct 5;264(28):16411–16420. [PubMed] [Google Scholar]
  79. de Jong S., Kooistra A. J., de Vries E. G., Mulder N. H., Zijlstra J. G. Topoisomerase II as a target of VM-26 and 4'-(9-acridinylamino)methanesulfon-m-aniside in atypical multidrug resistant human small cell lung carcinoma cells. Cancer Res. 1993 Mar 1;53(5):1064–1071. [PubMed] [Google Scholar]

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