Summary
Addition of N6,O2′-Dibutyryladenosine cyclic 3′,5′ monophosphate (DB cyclic AMP) plus theophylline or transfer to medium containing 0.2% serum slowed the growth of cultured mouse mastocytoma cells and eventually arrested their growth in G1 phase. Examination of the properties of cells arrested by either procedure suggested that the drugs arrested cells in G1 phase 1.5–2 h after the point of low serum arrest. Cycloheximide prevented the recovery of cell growth after low serum or drug-induced arrest demonstrating that protein synthesis was necessary to pass either growth restriction point. Cordycepin also prevented drug-arrested cells from progressing into cycle indicating a requirement for RNA synthesis to overcome the drug-induced growth arrest. Evidence is also presented that DB cyclic AMP prevented the cells receiving a pulse of calcium necessary to proceed past the DB cyclic AMP-sensitive growth restriction point. It is suggested that high cyclic AMP levels prevent mastocytoma cells from receiving a surge of calcium in G1 phase that is necessary if the cells are to proceed to S phase and eventually divide.
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Abbreviations
- DB cyclic AMP:
-
N6,O2′-dibutyryl-adenosine cyclic 3′,5′ monophosphate
- cyclic AMP:
-
adenosine cyclic 3′,5′ monophosphate
References
Abell, C. W. and Monahan, T. M., 1973. Cell Biol. 59: 549–558.
Pastan, I. H., Johnson, G. S. and Anderson, W. B., 1975. Ann. Rev. Biochem. 44: 491–522.
Berridge, M. J. and Rapp, P., 1977. In: Cyclic 3′,5′ nucleotides: mechanisms of action (Cramer, H. and Schultz, T., eds) pp. 65–76, J. Wiley and Sons, New York.
Schönhofer, T. S., and Peters, H. D., 1977. In: Cyclic 3′,5′ nucleotides: mechanisms of action (Cramer, H. and Schultz, T., eds) pp. 107–126, J. Wiley and Sons, New York.
Pardee, A. B., Dubrow, R., Hamlin, J. L. and Kletzien, R. F., 1978. Ann. Rev. Biochem. 47: 715–750.
Nomura, K., Hoshimo, T., Knebel, K. and Barker, M., 1978. In vitro 14: 174–179.
Keller, R. and Keist, R., 1973. Life Sciences 12: 97–105.
Thomas, D. B., Medley, G. and Lingwood, C. A., 1973. J. Cell. Biol. 57: 397–405.
Lingwood, C. A. and Thomas, D. B., 1974. J. Natl. Cancer Inst., 52: 1659–1664.
Davis, J. and Ralph, R. K., 1975. Cancer Res. 35: 1495–1504.
Granner, D. K., 1974. Arch. Biochem. Biophys. 165: 359–368.
Goldberg, M. C., Burke, G. C. and Morris, H. P., 1975. Biochem. Biophys. Res. Commun. 62: 320–327.
Coffino, P., Gray, I. W. and Tomkins, G. M., 1975. Proc. Natl. Acad. Sci, USA 72: 878–882.
Thomas, D. B., 1977. Biochem. Soc. Transact, 5: 1801–1808.
Smith, J. A. and Martin, L., 1973. Proc. Natl. Acad. Sci. USA, 70: 1263–1267.
Shields, P., Brooks, R. F., Riddle, P. N., Cappelaro, D. F. and Delia, D., 1978. Cell 15: 469–474.
Pardee, A. B., 1974. Proc. Natl. Acad. Sci. USA, 71: 1286–1290.
Yen, A. and Pardee, A. B., 1978. Exp. Cell. Res. 114: 389–395.
Kohn, A., 1975. Exp. Cell. Res. 94: 15–22.
Enger, M. D. and Tobey, R. A., 1972. Biochemistry 11: 269–277.
Bantock, C. R. and Price, D. J., 1975. Laboratory Manual of Cell Biology (Hall, D. and Hawkins, J., eds) pp. 79–85, The English University Press Ltd., London.
Miller, R. G. and Phillips, R. A., 1969. J. Cell Physiol. 73: 191–202.
Morgan, A. R. and Pulleyblank, D. E., 1974. Biochem. Biophys. Res. Commun. 61: 396–403.
Kram, R., Mamont, P. and Tomkins, G. M., 1973. Proc. Natl. Acad. Sci. USA, 70: 1432–1436.
Seifert, N. and Paul, D., 1972. Nature New Biol. 240: 281–283.
Otten, J. G., Johnson, G. S. and Pastan, I., 1972. J. Biol. Chem. 247: 7082–7087.
Yen, A. and Pardee, A. B., 1978. Exp. Cell Res. 116: 103–113.
Rossow, P., Riddle, V. G. H. and Pardee, A. B., 1979. Proc. Natl. Acad. Sci. USA 76: 4446–4450.
Rasmussen, H. and Goodman, D., 1977. Physiol. Rev. 57: 421–509.
Tupper, J. T., Del Rosso, M., Hazelton, B. and Zorgniotti, R., 1978. J. Cell Physiol. 95: 71–84.
Schubert, D., Lacorbiere, M., Whitlock, C. and Stallamp, W., 1978. Nature 273: 718–723.
Wrenn, R. W. and Biddulph, D. M., 1979. J. Cyclic Nuc. Res. 5: 239–250.
Freedman, M. H., Raff, M. L. and Gomperts, B., 1975. Nature, 255: 378–382.
Whitfield, J., Boynton, A. L., Macmanus, J. P., Sikorska, M. and Tsang, B. K., 1979. Molec. Cell Biochem. 27: 155–179.
Schneiderman, M. H., Dewey, W. C. and Highfield, D. A., 1971. Exp. Cell. Res., 67: 147–155.
Highfield, D. P. and Dewey, W. C., 1972. Exp. Cell Res., 75: 314–320.
Prescott, D. M., 1976. Adv. Genetics, 18: 99–177.
Kishimoto, S. and Lieberman, I., 1964. Exp. Cell Res., 36, 92–101.
Kuo, J. F. and Greengard, P., 1969. Proc. Natl. Acad. Sci. USA, 64: 1349–1355.
Thomas, E. L., King, L. E. and Morrison, M., 1979. Arch. Biochem. Biophys., 196: 459–464.
Le Peuch, C. J., Haiech, J. and Demaille, J. G., 1979. Biochemistry 18: 5150–5157.
Treiman, M., Pødenphant, J., Saermar, T. and Bock, E., 1979. FEBS Letts. 97: 147–150.
Varsanyi, M. and Heilmeyer, L. M. G., 1979. Biochemistry 18: 4869–4885.
Titanyi, V. P. K., 1974. Biochim. Biophys. Acta., 481: 140–151.
Sieghart, W., Theoharides, T. C., Alper, S. L., Douglas, W. W., and Greengard, P., 1978. Nature 275: 329–331.
Lala, P. K., 1972. Europ. J. Cancer, 8: 199–204.
Swierenga, S. H. H., Whitfield, J. F. and Karasaki, S., 1978. Proc. Natl. Acad. Sci. USA, 75: 6069–6071.
Paul, D. and Ristow, H. J., 1979. J. Cell Physiol., 98: 31–40.
Criss, W. E. and Morris, H. P., 1973. Biochem. Biophys. Res. Comm., 54: 380–386.
Granner, D. K., 1974. Arch. Biochem. Biophys. 165: 359–368.
Coffino, P., Gray, I. W. and Tomkins, G. M., 1975. Proc. Natl. Acad. Sci. USA 72: 878–882.
Cho-Chung, Y. S. and Clair, T., 1976. Nature, 265: 452–454.
Goldberg, M. C., Burke, G. C. and Morris, H. P., 1975. Biochem. Biophys. Res. Comm. 62: 320–327.
Collett, M. S. and Erikson, R. L., 1978. Proc. Natl. Acad. Sci. USA, 75: 2021–2024.
Griffin, J. D., Spangler, G. and Livingston, D. M., 1979. Proc. Natl. Acad. Sci. USA, 76: 2610–2614.
Stiles, C. D., Capone, G. T., Scher, C. D., Antoniades, H. N. van Wyk, J. J. and Pledger, W. J., 1979. Proc. Natl. Acad. Sci. USA, 76: 1279–1283.
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Knightbridge, A., Ralph, R.K. The control of growth of mouse mastocytoma Cells by N6,O2′-dibutyryladenosine cyclic 3′,5′-monophosphate. Mol Cell Biochem 34, 153–164 (1981). https://doi.org/10.1007/BF02359620
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DOI: https://doi.org/10.1007/BF02359620