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Increased intracellular phosphoribosylpyrophosphate and accelerated orotic acid decarboxylation in a mouse cell line resistant to purine and pyrimidine ribonucleosides

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Somatic Cell Genetics

Abstract

A line of mouse fibroblasts (A9AU-1), originally selected for growth in the presence of 6-azauridine, has been found to be resistant to cytotoxic concentrations of adenosine, guanosine, and thymidine. A9AU-1 cells convert orotic acid to uridine 5′-monophosphate at twice the rate of the A9P line from which the A9AU-1 clone was selected. The resistant cells also excrete purines, synthesized de novo, into the medium at an increased velocity. The average intracellular 5-phosphoribosyl-1-pyrophosphate (PRPP) concentration of the resistant line is 45% higher than that of the parental line. The elevated PRPP concentration is likely to be responsible for both the apparent acceleration of pyrimidine synthesis and the increased excretion of purines into the growth medium; it might also account, by one of the several possible mechanisms, for the resistance of the cells to cytotoxic concentrations of the various nucleo sides.

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Literature cited

  1. Pinsky, L., and Krooth, R. S. (1967).Proc. Natl. Acad. Sci. USA 57:1267–1274.

    PubMed  Google Scholar 

  2. Pasternak, C. A., and Handschumacher, R. E. (1959).J. Biol. Chem. 234:2992–2997.

    PubMed  Google Scholar 

  3. Handschumacher, R. E. (1960).J. Biol. Chem. 235:2917–2919.

    PubMed  Google Scholar 

  4. Ishii, K., and Green, H. (1973).J. Cell Sci. 13:429–439.

    PubMed  Google Scholar 

  5. McBurney, M. W., and Whitmore, G. F. (1975).J. Cell. Physiol. 85:87–100.

    PubMed  Google Scholar 

  6. Green, C. D., and Martin, D. W. (1973).Proc. Natl. Acad. Sci. USA 70:3698–3702.

    PubMed  Google Scholar 

  7. Hershko, A., Razin, A., and Mager, J. (1969).Biochim. Biophys. Acta 184:64–76.

    PubMed  Google Scholar 

  8. Roth, D. G., and Deuel, T. F. (1974).J. Biol. Chem. 249:297–301.

    PubMed  Google Scholar 

  9. Fox, I. H., and Kelley, W. N. (1972).J. Biol. Chem. 247:2126–2131.

    PubMed  Google Scholar 

  10. Becker, M. A., Kostel, P. J., and Meyer, L. J. (1975).J. Biol. Chem. 250:6822–6830.

    PubMed  Google Scholar 

  11. Hashmi, S., May, S. R., Krooth, R. S., and Miller, O. J. (1975).J. Cell. Physiol. 86:191–200.

    PubMed  Google Scholar 

  12. Littlefield, J. (1964).Nature 203:1142–1144.

    PubMed  Google Scholar 

  13. Cox, R. P., Krauss, M. R., Balis, M. E., and Dancis, J. (1972).Exp. Cell Res. 74:251–268.

    PubMed  Google Scholar 

  14. Szybalska, E. H., and Szybalski, W. (1962).Proc. Natl. Acad. Sci. USA 48:2026–2034.

    PubMed  Google Scholar 

  15. Hayflick, L. (1973). InTissue Culture: Methods and Applications, (eds.) Kruse, P. F., and Patterson, M. K., pp. 722–728. Academic Press, New York.

    Google Scholar 

  16. Thompson, E. B., Tomkins, G. M., and Curran, J. F. (1966).Proc. Natl. Acad. Sci. USA 56:296–303.

    PubMed  Google Scholar 

  17. Krooth, R. S., Pan, Y.-L., and Pinsky, L. (1973).Biochem. Genet. 8:133–148.

    PubMed  Google Scholar 

  18. Martin, D. W., and Owen, N. T. (1972).J. Biol. Chem. 247:5477–5485.

    PubMed  Google Scholar 

  19. Wood, A. W., Becker, M. A., Minna, J. D., and Seegmiller, J. E. (1973).Proc. Natl. Acad. Sci. USA 70:3880–3883.

    PubMed  Google Scholar 

  20. Church, R. B., and Robertson, F. W. (1966).J. Exp. Zool. 162:337–352.

    Google Scholar 

  21. Ashwell, G. (1957). InMethods in Enzymology, (eds.) Colowick, S. P., and Kaplan, N. O. Vol. 3, pp. 87–90, Academic Press, New York.

    Google Scholar 

  22. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951).J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  23. Chasin, L. A. (1974).Cell 2:37–41.

    PubMed  Google Scholar 

  24. Kelley, W. N., Beardmore, T. D., Fox, I. H., and Meade, J. C. (1971).Biochem. Pharmacol. 20:1471–1478.

    Google Scholar 

  25. Worthy, T. E., Grobner, W., and Kelley, W. N. (1974).Proc. Natl. Acad. Sci. USA 71:3031–3035.

    PubMed  Google Scholar 

  26. Kelley, W. N., and Beardmore, T. D. (1970).Science 169:388–390.

    PubMed  Google Scholar 

  27. Krystal, G., and Scholefield, P. G. (1973).Can. J. Biochem. 51:379–389.

    PubMed  Google Scholar 

  28. Herrmann, E. C., Dunn, J. H., and Schmidt, R. R. (1973).Anal. Biochem. 53:478–483.

    PubMed  Google Scholar 

  29. Kornberg, A., Lieberman, I., and Simms, E. S. (1955).J. Biol. Chem. 215:389–402.

    PubMed  Google Scholar 

  30. Reem, G. H. (1975).Science 190:1098–1099.

    PubMed  Google Scholar 

  31. May, S. R., and Krooth, R. S. (1976).Anal. Biochem. 75:389–401.

    PubMed  Google Scholar 

  32. Bennett, L. L., Jr., Schnebli, H. P., Vail, M. H., Allan, P. W., and Montgomery, J. A. (1966).Mol. Pharmacol. 2:432–443.

    PubMed  Google Scholar 

  33. Chan, T. A., Ishii, K., Long, C., and Green, H. (1973).J. Cell. Physiol. 81:315–322.

    PubMed  Google Scholar 

  34. Caldwell, I. C., Henderson, J. F., and Paterson, A. R. P. (1969).Can. J. Biochem. 45:735–744.

    Google Scholar 

  35. Medrano, L., and Green, H. (1974).Cell 1:23–26.

    Google Scholar 

  36. Krooth, R. S. (1964).Cold. Spr. Harb. Symp. Quant. Biol. 29:189–212.

    Google Scholar 

  37. Anderson, E. P., and Brockman, R. W. (1964).Biochim. Biophys. Acta 91:380–386.

    PubMed  Google Scholar 

  38. Lucas, Z. J. (1967).Science 156:1237–1240.

    PubMed  Google Scholar 

  39. Lineweaver, H., and Burke, D. (1934).J. Am. Chem. Soc. 56:658–666.

    Google Scholar 

  40. Pinsky, L., and Krooth, R. S. (1967).Proc. Natl. Acad. Sci. USA 57:925–932.

    PubMed  Google Scholar 

  41. Becker, M. A., Meyer, L. J., Wood, A. W., and Seegmiller, J. E. (1973).Science 179:1123–1126.

    PubMed  Google Scholar 

  42. Sperling, O., Persky-Brosh, S., Boer, P., and DeVries, A. (1973).Biochem. Med. 7:389–395.

    PubMed  Google Scholar 

  43. Becker, M. A., Meyer, L. J., and Seegmiller, J. E. (1973).Am. J. Med. 55:232–242.

    PubMed  Google Scholar 

  44. Greene, M. S., and Seegmiller, J. E. (1969).Arthritis Rheum. 12:666–667.

    Google Scholar 

  45. Shin, S. I. (1974).J. Cell Sci. 14:235–251.

    PubMed  Google Scholar 

  46. Wuu, K., and Krooth, R. S. (1968).Science 160:539–541.

    PubMed  Google Scholar 

  47. Krooth, R. S. (1970).Symp. Int. Soc. Cell Biol. 9:43–68.

    Google Scholar 

  48. Graf, L. H., Jr., McRoberts, J. A., Harrison, T. M., and Martin, D. W., Jr. (1976).J. Cell. Physiol. 88:331–342.

    PubMed  Google Scholar 

  49. Martin, D. W., Jr., and Maler, B. A. (1976).Science 193:408–411.

    PubMed  Google Scholar 

  50. Friedman, T., Seegmiller, J. E., and Subak-Sharpe, J. H. (1969).Exp. Cell Res. 56:425–429.

    PubMed  Google Scholar 

  51. Hilz, H., and Kaukel, E. (1973).Mol. Cell. Biochem. 1:229–239.

    PubMed  Google Scholar 

  52. Tax, W. J. M., Veerkamp, J. H., Trijbels, F. J. M., and Schretlen, E. D. A. M. (1976).Biochem. Pharmacol. 25:2025–2032.

    PubMed  Google Scholar 

  53. Jones, M. E. (1972). InCurrent Topics in Cellular Regulation, (eds.) Horecker, B. L., and Stadtman, E. R., Vol. 6, pp. 227–265, Academic Press, New York.

    Google Scholar 

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Authors and Affiliations

  1. Department of Human Genetics and Development, College of Physicians and Surgeons, Columbia University, 10032, New York, New York

    S. Randolph May, Shahnaz Hashmi, Orlando J. Miller & Robert S. Krooth

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  1. S. Randolph May
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  2. Shahnaz Hashmi
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  3. Orlando J. Miller
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  4. Robert S. Krooth
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May, S.R., Hashmi, S., Miller, O.J. et al. Increased intracellular phosphoribosylpyrophosphate and accelerated orotic acid decarboxylation in a mouse cell line resistant to purine and pyrimidine ribonucleosides. Somat Cell Mol Genet 3, 263–280 (1977). https://doi.org/10.1007/BF01538745

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  • DOI: https://doi.org/10.1007/BF01538745

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