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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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

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.[1]

References

  1. Synergistic effect of 3'-deoxyadenosine N1-oxide and adenosine deaminase inhibitors on growth of Ehrlich ascites tumor cells in vivo. Svendsen, K.R., Overgaard-Hansen, K., Frederiksen, S. Cancer Chemother. Pharmacol. (1988) [Pubmed]
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