Abstract
A cross has been performed between dedifferentiated rat hepatoma cells and the differentiated cells from which they were derived. 10 hybrid clones, containing the complete chromosome sets of both parents, show extinction of 4 liver-specific enzymes: tyrosine aminotransferase (E.C. 2.6.1.5), alanine aminotransferase (E.C. 2.6.1.2), and the liver-specific isozymes of alcohol dehydrogenase (E.C. 1.1.1.1) and aldolase (E.C. 4.1.2.13). Moreover, the 4 hybrid clones examined do not produce albumin. The only function of the differentiated parent which is not extinguished in the hybrid cells is inducibility of the aminotransferases. For 3 of the hybrid clones, extinction of 3 of the 4 enzymes is incomplete, but these clones do not differ in modal chromosome number from those which show more complete extinction of the enzymes. Subcloning of several of the hybrids revealed that the phenotype of the hybrids is very stable; 4 subclones showing reexpression of intermediate levels of the enzymes are characterized. These results show that dedifferentiation of the parental cells is not due to the simple loss of some factor required for the maintenance of expression of differentiated functions, and suggest that dedifferentiation is due to the activation of some control mechanism, whose final effect is negative, and which may be a part of the epigenotype of the embryonic hepatocyte.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Literature cited
Deschatrette, J., and Weiss, M. C. (1975).Biochimie 56:1603–1611.
Pilot, H. C., Peraino, C., Morse, P. A., and Potter, V. A. (1964).Natl. Cancer Inst. Monogr. 13:229–242.
Coon, H. G., and Weiss, M. C. (1969).Proc. Natl. Acad. Sci. U.S.A. 66:1220–1227.
Ham, R. G. (1965).Proc. Natl. Acad. Sci. U.S.A. 53:288–293.
Weiss, M. C., and Chaplain, M. (1971).Proc. Natl. Acad. Sci. U.S.A. 68:3026–3030.
Littlefield, J. (1964).Science 145:709–710.
Davidson, R. L., and Ephrussi, B. (1965).Nature 205:1170–1171.
Schneider, J. A., and Weiss, M. C. (1971).Proc. Natl. Acad. Sci. U.S.A. 62:852–859.
Sparkes, R. S., and Weiss, M. C. (1973).Proc. Natl. Acad. Sci. U.S.A. 70:377–381.
Bertolotti, R., and Weiss, M. C. (1972).J. Cell. Physiol. 79:211–223.
Bertolotti, R., and Weiss, M. C. (1972).Biochimie 54:195–201.
Diamonstone, T. I. (1966).Anal. Biochem. 16:395–401.
Segal, H. L., and Matsuzawa, T. (1970). In Colowick, S. P. and Kaplan, N. O. (eds.),Methods in Enzymology, Vol. 17a, Academic Press, New York, pp. 153–159.
Ohno, S., Stenius, C., Christian, L., Harris, C., and Yvey, C. (1970).Biochem. Genet. 4:565–577.
Koen, A. L., and Shaw, C. R. (1966).Biochem. Biophys. Acta 128:48–54.
Blostein, R., and Rutter, W. J. (1963).J. Biol. Chem. 238:3280–3285.
Penhoet, E. D., Rajkumar, T., and Rutter, W. J. (1966).Proc. Natl. Acad. Sci. U.S.A. 56:1275–1282.
Glock, G. E., and McLean, P. (1953).Biochemistry 55:400–408.
Meera Khan, P. (1971).Arch. Biochem. Biophys. 145:470–483.
Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J. (1951).J. Biol. Chem. 193:265–275.
Malawista, S. E., and Weiss, M. C. (1974)Proc. Natl. Acad. Sci. U.S.A. 71:927–931.
Peterson, J., and Weiss, M. C. (1971).Proc. Natl. Acad. Sci. U.S.A. 69:571–575.
Weiss, M. C., Sparkes, R. S., and Bertolotti, R. (1975).Somatic Cell Genet. 1:27–40.
Paul, J., and Hickey, I. (1974).Exp. Cell. Res. 87:20–30.
Bertolotti, R., and Weiss, M. C. (1974).Differentiation 2:5–17.
Ephrussi, B. (1972).Hybridization of Somatic Cells, Princeton University Press, Princeton, New Jersey.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deschatrette, J., Weiss, M.C. Extinction of liver-specific functions in hybrids between differentiated and dedifferentiated rat hepatoma cells. Somat Cell Mol Genet 1, 279–292 (1975). https://doi.org/10.1007/BF01538451
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01538451