Abstract
Adenosine exerts marked cytostatic and cytotoxic actions to mammalian cells. The nucleoside has been reported to inhibit pyrimidine nucleotide synthesis, to foster cyclic AMP accumulation and to cause the accumulation of S-adenosylhomocysteine (AdoHcy).1,2 Adenosine kinase (EC 2.7.1.20) deficient mammalian cells do not phosphorylate adenosine, but adenosine still blocks their growth, and this Is not reversed by addition of uridine. 2,3 Thus, adenosine may exert toxicity at the nucleoside level. Also, some adenosine analogs are cytotoxic without being converted to nucleotides.4
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
J. F. Henderson and F. W. Scott, Inhibition of animal and invertebrate cell growth by naturally occurring purine bases and ribonucleosides, Pharmacol. Ther. 8: 539 (1980).
N. M. Kredlch and M. S. Hershfield, S-adenosylhomocysteine toxicity In normal and adenosine kinase-deficient lymphoblasts of human origin, Proc. Natj Acad. Sci. USA 76: 2450 (1979).
M. Kubota, N. Kamatani, P. E. Daddona, and D. A. Carson, Character-ization of an adenosine deaminase-deficient human histiocytic lymphoma cell line (DHL-9) and selection of mutants deficient In adenosine kinase and deoxycytidine kinase, Cancer Res. 43: 2606 (1983).
J. A. Montgomery, S. J. Clayton, H. J. Thomas, W. M. Shannon, G. Arnett, A. J. Bodner, I.-K. Kion, G. L. Cantoni, and P. K. Chiang, Carbocyclic analogue of 3-deazaadenosine: A novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target, J. Med Chem 25: 626 (1982).
E. O. Kajander, M. Kubota, C. J. Carrera, J. A. Montgomery and D. A. Carson, Multiple drug resistance In mutant lymphoblasts with enlarged S-adenosylmethionine pools, submitted for publication.
T. P. Zimmerman, G. Wolberg, G. S. Duncan, and G. B. Elion, Adenosine analogues as substrates and Inhibitors of S-adenosylhomo-cysteine hydrolase In intact lymphocytes, Biochem. 19: 2252 (1980).
R. T. Borchardt, B. T. Keller, and U. Patel-Thombre, Neplanocin A. A potent Inhibitor of S-adenosyhomocysteine hydrolase and of vaccinia virus multiplication In mouse L929 cells, J. Biol. Chem. 259: 4353 (1984).
R. I. Glazer and M. C. Knode, Neplanocin A. A cyclopentenyl analog of adenosine with specificity for Inhibiting RNA methylation, J. Biol. Chem. 259: 12964 (1984).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Kajander, E.O., Kubota, M., Willis, E.H., Carson, D.A. (1986). S-Adenosylmethionine Metabolism as a Target for Adenosine Toxicity. In: Nyhan, W.L., Thompson, L.F., Watts, R.W.E. (eds) Purine and Pyrimidine Metabolism in Man V. Advances in Experimental Medicine and Biology, vol 195B. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-1248-2_33
Download citation
DOI: https://doi.org/10.1007/978-1-4684-1248-2_33
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4684-1250-5
Online ISBN: 978-1-4684-1248-2
eBook Packages: Springer Book Archive