Abstract
Hydroxyurea, when injected intraperitoneally at a dose of 1 mg/g body weight, inhibited thymidine kinase activity in developing rat cerebrum (16-day-embryonic) and cerebellum (7-day-postnatal) within a few hours of administration. The inhibition was time-dependent and both cytosolic and mitochondrial thymidine kinases were affected. Under the same conditions, the activities of certain other enzymes concerned with DNA metabolism,viz., DNA polymerase, and acid and alkaline DNases were not inhibited. Further, the addition of hydroxyureain vitro had no effect on the activity of any of the enzymes studied. However, similar treatment given to 2-year-old rat failed to exert any inhibition on either the mitochondrial or soluble thymidine kinase activities in grey and white matter regions of cerebrum and cerebellum. It is inferred that hydroxyurea, apart from its already known effect on ribonucleotide reductase of replicating cells, also affects thymidine kinase.
Similar content being viewed by others
Abbreviations
- CNPase:
-
2′,3′-Cyclic nucleotide 3′-phosphohydrolase
- SDH:
-
succinic dehydrogenase
References
Andrae, U. and Ziegler-Skylakakis, K. (1984)Mutat. Res.,130, 227.
Berk, A. J. and Clayton, D. A. (1973)J. Biol Chem.,248, 2722.
Bollum, F. J. and Potter, V. R. (1959)Cancer Res.,19, 561.
Brent, T. P. (1971)Cell Tissue Kinet.,4, 297.
Bresnick, E. (1978)Methods Enzymol.,51, 500.
Koch, J. and Stockstad, E. L. R. (1967)Eur. J. Biochem.,3, 1.
Kurihara, T. and Tsukada, Y. (1967)J. Neurochem.,14, 1167.
Kyaw, A., Maung-U, K. and Toe, T. (1985)Anal. Biochem.,145, 230.
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. (1951)J. Biol Chem.,193, 265.
Magrath, I. T., Mugerwa, J., Bailey, I., Olweny, C. and Kiryabwire, Y. (1974)Q. J. Med.,43, 481.
Masui, H. and Garren, L. D. (1971)J. Biol, Chem.,246, 5407.
Mira Kaplay, Prabhakar, V. and Subba Rao K., (1983)Biochem. Int.,6, 473.
Morton, R. K. (1955)Methods Enzymol,1, 25.
Nachlas, M. M., Margulies, S. I. and Seligman, A. M. (1960)J. Biol. Chem.,235, 499.
Philips, F. S., Sternberg, S. S., Schwartz, H. S., Cronin, A. P., Sodergen, J. E. and Vidal, P. M. (1967)Cancer Res.,27, 61.
Prabhakar, V., Mira Kaplay and Subba Rao, K. (1984)Biochem. Int.,8, 409.
Prabhakar, V., Subrahmanyam, K., Subba Rao, K. V. and Subba Rao K., (1987)Indian J. Biochem. Biophys.,24, 29.
Prohaska, J. R., Clark, D. A. and Wells, W. W. (1973)Anal. Biochem.,56, 275:
Rabes, H. M., Iseler, G., Tuczek, H. V. and Kerler, R. (1974)Experientia 30, 1116.
Slor, H., Bustan, H. and Lev., T. (1973)Biochem. Biophys. Res. Commun.,52, 556.
Subba Rao, K. V. and Subba Rao K., (1982)Mech Ageing Dev.,18, 225.
Subba Rao, K. V. and Subba Rao K., (1984)Biochem. Int.,9, 391.
Susheela, L. and Ramasarma, T. (1971)Biochim. Biophys. Acta.,242, 532.
Timson, J. (1975)Mutat. Res.,32, 115.
Vilenchik, M. M. and Tretjak, T. M. (1977)J. Neurochem.,18, 1159.
Yamada, N., Sawasaki, Y. and Nakajima, H. (1979)Brain Res.,168, 393.
Yamada, N., Sawasaki, Y. and Nakajima, H. (1980)Brain Res.,195, 485.
Young, C. W. and Hodas, S. (1964)Science,146, 1172.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Prabhakar, V., Rao, K.S. Effect of hydroxyurea on subcellular activities of thymidine kinase in developing and aging rat brain. J Biosci 13, 1–7 (1988). https://doi.org/10.1007/BF02832206
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02832206