Synergistic effect of 3'-deoxyadenosine N1-oxide and adenosine deaminase inhibitors on growth of Ehrlich ascites tumor cells in vivo.

Abstract

The simultaneous administration of 3'-deoxyadenosine N1-oxide (3'-dANO) and the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) or 2'-deoxycoformycin (2'-dCF) to mice bearing Ehrlich ascites tumor cells resistant to 3'-dANO resulted in 80%-90% inhibition of tumor growth in vivo. 3'-dANO and 2'-dCF increased the survival time of tumor-bearing mice by a factor of 2. In vitro studies showed that the 3'-dANO resistant Ehrlich cells initiate the metabolism of 3'-dANO by a reduction to 3'-deoxyadenosine, which is converted primarily to 3'-deoxyinosine by adenosine deaminase and, to a small extent, phosphorylated to the cell toxic agent 3'-dATP. By the addition of EHNA or 2'-dCF it was possible to block the formation of 3'-deoxyinosine, resulting in a profound stimulation in the accumulation of 3'-dATP. The development of resistance to 3'-dANO was studied in cell cultures and found to be accompanied by changes in the enzyme activities of the reductase, the adenosine kinase, and the adenosine deaminase.

• Authors: K R Svendsen, K Overgaard-Hansen, S Frederiksen
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 21 Issue 1 Pg. 35-9 ( 1988) ISSN: 0344-5704 [Print] Germany
• PMID: 3257721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine Deaminase Inhibitors
• Antineoplastic Agents
• Deoxyadenine Nucleotides
• Deoxyadenosines
• Ribonucleosides
• 3'-deoxyadenosine N(1)-oxide
• Coformycin
• Pentostatin
• 9-(2-hydroxy-3-nonyl)adenine
• 3'-deoxyadenosine 5'-triphosphate
• Nucleoside Deaminases
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Adenosine Deaminase Inhibitors
• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Ehrlich Tumor (drug therapy)
• Coformycin (analogs & derivatives, pharmacology)
• Deoxyadenine Nucleotides (metabolism)
• Deoxyadenosines (analogs & derivatives, therapeutic use)
• Drug Resistance
• Drug Synergism
• Female
• Mice
• Nucleoside Deaminases (antagonists & inhibitors)
• Pentostatin
• Ribonucleosides (pharmacology)