Deoxyadenosine triphosphate accumulation in erythrocytes of deoxycoformycin-treated mice.
The accumulation of deoxyadenosine triphosphate (dATP) in erythrocytes of mice treated with the adenosine deaminase inhibitor deoxycoformycin was studied in an attempt to establish and evaluate a model system for the study of at least some biochemical aspects of hereditary adenosine deaminase deficiency. Mouse erythrocytes in vitro readily phosphorylated deoxyadenosine to dATP, and this nucleotide was relatively stable once formed. dATP accumulated in vivo in mice treated with deoxycoformycin both as a function of dose from 0.25 to 10 mg/kg, and with time after administration. Major sources of the deoxyadenosine used for dATP formation in vivo appear to be normoblast nuclei produced during erythropoiesis, and dying cells; minor sources would appear to include dietary DNA, overproduction of deoxyribonucleotides, and DNA repair.
D000243:Adenosine Deaminase / Q000172:deficiency; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003838:Deoxyadenine Nucleotides / Q000097:blood*; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism*; D051379:Mice; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*
D058892:Adenosine Deaminase Inhibitors; D003838:Deoxyadenine Nucleotides; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; C026600:2'-deoxyadenosine triphosphate