B cells as well as T cells form deoxynucleotides from either deoxyadenosine or deoxyguanosine.
Enzyme inhibitors used to simulate the inherited immunodeficiency diseases, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency, have been assessed in cultured human lymphocytes. Only 2'-deoxycoformycin (dCF) completely inhibited ADA in T and B cells at concentrations in excess of 5 microM. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and 8-amino guanosine (8-NH2GR) did not inhibit ADA or PNP completely at any concentration. Detailed metabolic experiments comparing viability and deoxynucleotide accumulation showed that B cell lines of malignant origin also accumulated high levels of dATP from 2'-deoxyadenosine (dAR), and dGTP from 2'-deoxyguanosine (dGR) as effectively as T cells--even without inhibitors, however, dAR reduced cell viability only when ADA was inhibited by dCF, whilst dGR was equally toxic with or without inhibitor, even to a line which accumulated no dGTP. These experiments indicate that cultured lymphocytes, using either EHNA or 8-NH2GR as enzyme inhibitor, are not valid models of the toxicity to the immune system in inherited ADA or PNP deficiency. They demonstrate that the ability to accumulate high levels of dATP or dGTP is not exclusive to T cells and that the in vitro toxicity of dAR or dGR could relate to the use of excess substrate and/or accumulation in different nucleotide, not deoxynucleotide pools.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D003838:Deoxyadenine Nucleotides / Q000096:biosynthesis; D003839:Deoxyadenosines / Q000378:metabolism*; D003848:Deoxyguanine Nucleotides / Q000096:biosynthesis; D003849:Deoxyguanosine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015649:Pentostatin; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000378:metabolism*
D058892:Adenosine Deaminase Inhibitors; D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D003848:Deoxyguanine Nucleotides; D003070:Coformycin; D006151:Guanosine; C032533:8-aminoguanosine; D015649:Pentostatin; C010192:9-(2-hydroxy-3-nonyl)adenine; C029603:deoxyguanosine triphosphate; D011683:Purine-Nucleoside Phosphorylase; D003849:Deoxyguanosine; D000225:Adenine; C026600:2'-deoxyadenosine triphosphate