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Collateral sensitivity of a methotrexate-resistant L1210 cell line to the vinca alkaloids

  • Original Articles
  • Methotrexate, L1210, Vinca Alkaloids
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Summary

L1210 mouse leukaemia cell lines showing a 20,000-fold differential sensitivity to methotrexate have been shown to exhibit some collateral sensitivity to at least two of the vinca alkaloids, vinblastine and vindesine. Vinblastine is the more cytotoxic for both cell lines. The extent of the collateral sensitivity decreases in the order vindesine>vinblastine >vincristine.

Total cellular uptake studies with radiolabelled methotrexate showed only a two- to three-fold greater incorporation in the sensitive line. On the other hand, a two-fold greater incorporation of labelled vincristine occurred in the resistant line. No significant difference in the uptake occurred following labelled vinblastine treatment by the two cell lines.

It is unlikely that differences in uptake account for the altered drug responses observed in the two cell lines.

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References

  1. Albrecht AM, Biedler JL, Hutchison DJ (1972) Two different species of dihydrofolate reductase in mammalian cells differentially resistant to amethopterin and methasquin. Cancer Res 32:1539

    PubMed  Google Scholar 

  2. Alt FW, Kellems RE, Bertino JR, Schimke RT (1978) Selective multiplication of dihydrofolate reductase genes in methotrexate resistant variants of cultured murine cells. J Biol Chem 253:1357

    Google Scholar 

  3. Bagshawe KD (1969) Vinca alkaloids in the treatment of gestational choriocarcinoma. In: Shedden WI (ed) The vinca alkaloids in the chemotherapy of malignant diseases. Proceedings of the Symposium, London, p 61

  4. Bender RA, Bleyer WA, Frisby SA, Oliverio VT (1975) Alteration of methotrexate uptake in human leukaemia cells by other agents. Cancer Res 35:1305

    PubMed  Google Scholar 

  5. Bertino JR, Booth BA, Bieber AL, Cashmore A, Sartorelli AC (1964) Studies on the inhibition of dihydrofolate reductase by the folate antagonists. J Biol Chem 239:479

    Google Scholar 

  6. Bleyer WA, Frisby SA, Oliverio VT (1975) Uptake and binding of vincristine by murine leukaemia cells. Biochem Pharmacol 24:633

    Article  PubMed  Google Scholar 

  7. Bradner WT, Hutchison DH (1966) Necarcinostatin (NSC-69856): an antitumor antibiotic effective against ascitic leukaemia L1210 in mice. Cancer Chemother Rep 50:79

    PubMed  Google Scholar 

  8. Chellow PL, Sirotnak FM, Dorick DM, Moccio DM (1979) Schedule-dependent synergism of methotrexate and vincristine against murine L1210 leukaemia. Cancer Treat Rep 63:12

    Google Scholar 

  9. Chen T (1977) In situ detection of mycoplasma contamination in cell culture by fluorescent Hoechst 33258 stain. Exp Cell Res 104:255

    PubMed  Google Scholar 

  10. Creasey WA (1975) Vinca alkaloids and colchicine. In: Sartorelli AC, Johns DG (eds) Hdb Exp Pharmacol, vol XXXVIII/2. Springer, Berlin Heidelberg New York, p 670

    Google Scholar 

  11. Dano K (1973) Active outward transport of daunomycin in resistant Ehrlich ascites tumour cells. Biochim Biophys Acta 323:466

    PubMed  Google Scholar 

  12. Fox BW (1977) Collateral sensitivity between methylene dimethanesulphonate and halogenated methotrexate derivatives in the Yoshida sarcoma in vivo and in vitro. J Natl Cancer Inst 58:955

    PubMed  Google Scholar 

  13. Herman TS, Cress AE, Gerner EW (1979) Collateral sensitivity to methotrexate in cells resistant to adriamycin. Cancer Res 39:1937

    PubMed  Google Scholar 

  14. Hertz R, Lewis J, Lipsett MB (1961) Five years' experience with the chemotherapy of metastatic choriocarcinoma and related trophoblastic tumours in women. Am J Obstet Gynecol 82:631

    PubMed  Google Scholar 

  15. Hill BT, Whelan RDH (1981) Comparative cell killing and kinetic effects of vincristine or vindesine in mammalian cell lines. J Natl Cancer Inst. 67:437

    PubMed  Google Scholar 

  16. Hutchison DJ (1965) Studies on cross resistance and collateral sensitivity (1962–1964) Cancer Res 25:1581

    PubMed  Google Scholar 

  17. Hutchison DJ, Schmid FA (1973) Cross resistance and collateral sensitivity. In: Mihich E (ed) Drug resistance and selectivity: Biochemical and cellular basis. Academic Press, New York, p 73

    Google Scholar 

  18. Kaufmann RJ, Bertino JR, Schimke RT (1979) Quantitation of dihydrofolate reductase in individual parental and methotrexate resistant murine cells. J Biol Chem 253:5852

    Google Scholar 

  19. Madoc-Jones H, Mauro F (1968) Interphase action of vincristine and vinblastine: differences in their lethal action through the mitotic cycle of cultured mammalian cells. J Cell Physiol 72:185

    PubMed  Google Scholar 

  20. Paintrand M, Dantchev D, Pignot I, Bourut C, Reiss F, Mathé G (1981) Comparative actions of vindesine, vinblastine and vincristine: an electron microscopical study in mice using P388 leukaemia cells. Biol Cell 40:93

    Google Scholar 

  21. Poppitt DG, McGown AT, Fox BW (1984) The use of a fluorescent methotrexate probe to monitor the effects of three vinca alkaloids on a mixed population of parental L1210 and gene-amplified methotrexate resistant cells by flow cytometry. Cancer Chemother Pharmacol 13:54

    PubMed  Google Scholar 

  22. Rosner F, Hirshaut Y, Grunwald HW, Dieterich M (1975) In vitro combination chemotherapy demonstrating potentiation of vincristine cytotoxicity by prednisone. Cancer Res 35:700

    PubMed  Google Scholar 

  23. Rutman RJ (1964) Experimental chemotherapy studies. V. The collateral sensitivity to alkylating agents of several antimetabolite-resistant ascites tumours in mice. Cancer 24:634

    Google Scholar 

  24. Sirotnak FM, Kurita A, Hutchison DJ (1968) On the nature of a transport alteration determining resistance to amethopterin in L1210 leukaemia. Cancer Res 28:75

    PubMed  Google Scholar 

  25. Stryckman PA, Lurie PM, Manaster J, Vameoa G (1973) Mode of action of chemotherapy in vivo on human acute leukaemia. II. Vincristine. Eur J Cancer 9:613

    PubMed  Google Scholar 

  26. Zager RF, Frisby SA, Oliverio VT (1973) The effects of antibiotics of cancer chemotherapeutic agents on cellular transport and antitumour activity of methotrexate in L1210 murine leukaemia. Cancer Res 33:1670

    PubMed  Google Scholar 

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Poppitt, D.G., McGown, A.T. & Fox, B.W. Collateral sensitivity of a methotrexate-resistant L1210 cell line to the vinca alkaloids. Cancer Chemother. Pharmacol. 13, 43–46 (1984). https://doi.org/10.1007/BF00401446

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  • DOI: https://doi.org/10.1007/BF00401446

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