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Newly formed chromosome-like structures in independent mouse P388 sublines with developed in vivomdr1 gene amplification

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Somatic Cell and Molecular Genetics

Abstract

Mouse leukemia P388 sublines that aquired the resistance to multiple drugs as a result of treatment in vivo with anthracyclines (rubomycin, ruboxyl) and/or vincristine were studied. Themdr gene amplification was found in all tested cell lines: in four of five sublines all three members of themdr gene family showed increased copy numbers, and in one cell line, developed after treatment with ruboxyl,mdr1a andmdr1b genes were amplified to the same degree, whereas themdr2 gene was not amplified at all. The levels of amplification ofmdr genes varied in different cell lines from 30-fold to 50-fold. Unusual cytological manifestations—relatively large newly formed chromosomelike structures, were revealed in four of five long-term independent sublines. Some of these structures did not contained C blocks; the others, in contrast, were enriched by C-heterochromatin. In situ hybridization showed the presence ofmdr genes in newly formed bodies. In the majority of cases, the formation of chromosomelike structures was preceded by the appearance of other, smaller size, structures: the so-called “small chromatin bodies” (minichromosomes) and/or homogeneously G-positive small ring chromosomes.

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Literature cited

  1. Alitalo, K., and Schwab, M. (1986).Adv. Cancer Res. 47235–281.

    Google Scholar 

  2. Schwab, M., and Amler, L.C. (1990).Genes Chrom. Cancer 1181–193.

    Google Scholar 

  3. Stark, G.R., Debatisse, M., Giulotto, E., and Wahl, G.M. (1989).Cell 57901–908.

    Google Scholar 

  4. Stark, G.R. (1986).Cancer Surv. 51–23.

    Google Scholar 

  5. Schimke, R.T. (1984).Cell 37705–713.

    Google Scholar 

  6. Shen, D.W., Fojo, A., Chin, J.E., Roninson, I.B., Richert, N., Pastan, I., and Gottesman, M.M. (1986).Science 232643–645.

    Google Scholar 

  7. Van der Bliek, A.M., Baas, F., Van der Velde-Koerts, T., Biedler, J.L., Meyers, M.B., Ozols, R.F., and Hamilton, T.C. (1988).Cancer Res. 485927–5932.

    Google Scholar 

  8. Chin, J.E., Soffir, R., Noonan, K.E., Choi, K., and Roninson, I.B. (1989).Mol. Cell. Biol. 93808–3820.

    Google Scholar 

  9. Hsu, S.I., Lothstein, L., and Horwitz, S.B. (1989).J. Biol. Chem. 26412053–12062.

    Google Scholar 

  10. Ng, W.F., Sarangi, F., Zastawny, R.L., Weinot-Drebot, L., and Ling, V. (1989).Mol. Cell. Biol. 91224–1232.

    Google Scholar 

  11. Bradley, G., Juranka, P.F., and Ling, V. (1988).Biochim. Biophys. Acta 94887–128.

    Google Scholar 

  12. Gottesman, M.M., and Pastan, I. (1988).Trends Pharmacol. Sci. 954–58.

    Google Scholar 

  13. Croop, J.M., Gros, P., and Housman, D.E. (1988).J. Clin. Invest. 811303–1309.

    Google Scholar 

  14. Endicott, J.A., and Ling, V. (1989).Annu. Rev. Biochem. 58137–171.

    Google Scholar 

  15. Rothenberg, M., and Ling, V. (1989).J. Natl. Cancer Inst. 81907–910.

    Google Scholar 

  16. Juranka, P.F., Zastawny, R.L., and Ling, V. (1989).FASEB 32583–2592.

    Google Scholar 

  17. Van der Bliek, A.M., and Borst, P. (1989).Adv. Cancer Res. 52165–203.

    Google Scholar 

  18. Horns, R.C., Dower, W.J., and Schimke, R.T. (1984).J. Clin. Oncol. 22–7.

    Google Scholar 

  19. Trent, J.M., Buick, R.N., Olson, S., Horns, R.C., and Schimke, R.T. (1984).J. Clin. Oncol. 28–15.

    Google Scholar 

  20. Carman, M.D., Schornagel, J.H., Rivest, R.C., Srimatkandada, S., Portlock, C.S., Duffy, T., and Bertino, J.R. (1984).J. Clin. Oncol. 216–20.

    Google Scholar 

  21. Demidova, N.S., Goncharova, S.A., Chernova, O.B., Kopnin, B.P., and Gudkov, A.V. (1987).Genetika 231797–1806 (in Russian).

    Google Scholar 

  22. Gudkov, A.V., Chernova, O.B., Kazarov, A.R., and Kopnin, B.P. (1987).Somat. Cell Mol. Genet. 13609–619.

    Google Scholar 

  23. Goncharova, S.A., Demidova, N.S., Shiryaeva, O.A., Shevtsova, V.N., and Konovalova, N.P. (1987).Exp. Oncol. 942–46 (in Russian).

    Google Scholar 

  24. Shiryaeva, O.A., Demidova, N.S., Goncharova, S.A., and Konovalova, N.P. (1991).Exp. Oncol. (submitted) (in Russian).

  25. Seabright, M. (1971).Lancet 2971–972.

    Google Scholar 

  26. Sumner, A.T. (1972).Exp. Cell Res. 75304–306.

    Google Scholar 

  27. Ueda, K., Clark, D.P., Chen, C.-J., Roninson, I.B., Gottesman, M.M., and Pastan, I. (1987).J. Biol. Chem. 262505–508.

    Google Scholar 

  28. Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982).Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York).

    Google Scholar 

  29. Feinberg, A.P., and Vogelstein, B. (1983).Anal. Biochem. 1326–13.

    Google Scholar 

  30. Harper, M.E., and Saunders, G.F. (1981).Chromosoma 83431–439.

    Google Scholar 

  31. Kopnin, B.P., and Gudkov, A.V. (1982).Genetika 181683–1692 (in Russian).

    Google Scholar 

  32. Kopnin, B.P., Massino, J.S., and Gudkov, A.V. (1985).Chromosoma 9225–36.

    Google Scholar 

  33. Gudkov, A., and Kopnin, B. (1985).BioEssays 368–71.

    Google Scholar 

  34. Jakobsson, A.-M., Arnason, U., Levan, A., Martinsson, T., Hanson, C., and Levan, G. (1987).Chromosoma 95408–418.

    Google Scholar 

  35. Shen, D.W., Fojo, A., Chin, J.E., Roninson, I.B., Richert, N., Pastan, I., and Gottesman, M.M. (1986).Science 232643–645.

    Google Scholar 

  36. Bradley, G., Naik, M., and Ling, V. (1989).Cancer Res. 492790–2796.

    Google Scholar 

  37. Capranico, G., De Isabella, P., Castelli, C., Supino, R., Parmiani, G., and Zunino, F. (1989).Br. J. Cancer 59682–685.

    Google Scholar 

  38. Van der Bliek, A.M., Van der Velde-Koerts, T., Ling, V., and Borst, P. (1986).Mol. Cell. Biol. 61671–1678.

    Google Scholar 

  39. De Bruijn, M.H.L., Van der Bliek, A.M., Biedler, J.L., and Borst, P. (1986).Mol. Cell. Biol. 64717–4722.

    Google Scholar 

  40. Ståhl, F., Martinsson, T., Dahllof, B., and Levan, G. (1988).Hereditas 108251–258.

    Google Scholar 

  41. Emanuel, N., Konovalova, N., and Diatchkovskaya, —. (1985).Neoplasma 32285–289.

    Google Scholar 

  42. Sen, S., Teeter, L.D., and Kuo, T. (1987).Chromosoma 95117–125.

    Google Scholar 

  43. Trent, J., Bell, D., Willard, H., and Ling, V. (1985).Hum. Gene Mapping 8. Cytogenet. Cell Genet. 00:761–762.

    Google Scholar 

  44. Gudkov, A.V., Chernova, O.B., and Kopnin, B.P. (1990). InMolecular and Cellular Biology of Multidrug Resistance in Tumor Cells, (ed.) Roninson, I.B. (Plenum Publishing, New York), pp. 147–167.

    Google Scholar 

  45. Slovak, M.L., Hoeltge, G.A., and Trent, J.M. (1987).Cancer Res. 476646–6652.

    Google Scholar 

  46. Trent, J.M., Meltzer, P.S., Slovak, M.L., Hill, A.B., Dalton, W.S., Beck, W.T., and Coles, S.P.S. (1988). InMechanisms of Drug Resistance in Neoplastic Cells, (eds.) Wooley, P.V. and Tew, K.D. (Academic Press, New York), pp. 259–276.

    Google Scholar 

  47. Callen, D.F., Baker, E., Simmers, R.N., and Roninson, I.B. (1987).Hum. Genet. 77142–144.

    Google Scholar 

  48. Martinsson, T., and Levan, G. (1987).Cytogenet. Cell Genet. 4599–101.

    Google Scholar 

  49. Slovak, M.L., Lothstein, L., Horwitz, S.B., and Trent, J.M. (1988).Leukemia 2453–458.

    Google Scholar 

  50. Schwab, M., Ellison, J., Busch, M., Rosenau, W., Varmus, M.E., and Bishop, J.M. (1984).Proc. Natl. Acad. Sci. U.S.A. 814940–4944.

    Google Scholar 

  51. Kohl, N.E., Kanda, N., Schreck, R.R., Bruns, G., Latt, S.A., Gilbert, F., and Alt, F.W. (1983).Cell 35359–367.

    Google Scholar 

  52. Lin, C.C., Meyne, J., Sasi, R., and Moyzis, R.K. (1990).Cancer Genet. Cytogenet. 48271–274.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Chemical Physics at Chernogolovka, Academy of Sciences of the USSR, U.S.S.R.

    N. S. Demidova & A. S. Goncharova

  2. Institute of Cancerogenesis, All-Union Cancer Research Center, Kashirskoye shosse 24, 115478, Moscow, U.S.S.R.

    O. B. Chernova, E. Y. Siyanova & B. P. Kopnin

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  1. N. S. Demidova
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  2. O. B. Chernova
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  3. E. Y. Siyanova
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  4. A. S. Goncharova
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  5. B. P. Kopnin
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Demidova, N.S., Chernova, O.B., Siyanova, E.Y. et al. Newly formed chromosome-like structures in independent mouse P388 sublines with developed in vivomdr1 gene amplification. Somat Cell Mol Genet 17, 581–590 (1991). https://doi.org/10.1007/BF01233623

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  • DOI: https://doi.org/10.1007/BF01233623

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