Disease relevance of deoxyadenosine

• 5'-Iodotubercidin in nanomolar concentrations completely and dose-dependently inhibited formation of dATP and also protected against toxicity of submillimolar concentrations of dAdo in sympathetic neurons [1].
• In the present study we examined whether dAdo/dCF, can enhance the antitumor activity of CLB and 4-HC in chronic lymphocytic leukemia (CLL) cells in vitro [2].

High impact information on deoxyadenosine

• Because the orientations of the intercalated hydrocarbon are known from NMR solution structures of duplex oligonucleotides containing these dA adducts, a detailed analysis of the relationship between the position of intercalation and trapping of Top2 is possible [3].
• Of the deoxyribonucleosides, dGuo was the most potent cell growth inhibitor; however, the potency of added dAdo was probably attenuated by the presence of adenosine deaminase in the tissue culture growth medium [4].
• We investigated the mechanism of cell growth inhibition caused by the deoxyribonucleosides thymidine (dThd), deoxyguanosine (dGuo), deoxyadenosine (dAdo), and deoxycytidine (dCyd) [4].
• This differs from our previous observation that intercalating dA adducts derived from benzo[c]phenanthrene (BcPh) DEs inhibit WRN activity in a strand- and stereospecific manner [5].
• In support of such a mechanism we show that 2-deoxyadenosine (dAdo) induces apoptosis in chick embryonic sympathetic neurons supported in culture by NGF, excess K+, phorbol 12,13-dibutyrate, or forskolin [1].

Biological context of deoxyadenosine

• Supportive evidence for a central role of dATP was gained by inhibition of kinases necessary for phosphorylation of dAdo [1].
• In addition, a minor dGuo adduct derived from the bay-region syn-diol-epoxide of 7-MBA was detected as well as a minor dAdo adduct from this diol-epoxide [6].
• We have observed that deoxyadenosine (dAdo) plus dCF (dAdo/dCF) inhibit the repair of x-irradiation-induced and bleomycin-induced DNA damage in vitro, and that this results in either synergistic or additive cytotoxicity, respectively [2].

Anatomical context of deoxyadenosine

• Although some of these actions of dAdo were remarkably similar to those reported for human lymphoid cells, several were uniquely different [1].
• Incubation with dCF (10(-5)M) and dAdo (10(-4)M) for 18 hours, inhibited protein and RNA synthesis in unstimulated lymphocytes and impaired the ability of the cells to respond to PHA stimulation or to give rise to T-cell colonies in methyl-cellulose [7].

Associations of deoxyadenosine with other chemical compounds

• Finally, inhibition of adenosine deaminase by deoxycoformycin or erythro-9-(2-hydroxy-3-nonyl) adenine did not potentiate the toxic effects of dAdo [1].
• We have evaluated the effectiveness of two inhibitors of poly-ADP-ribosylation, nicotinamide and 3-aminobenzamide as rescue agents in resting and PHA-stimulated lymphocytes damaged by the combination of deoxycoformycin (dCF) plus deoxyadenosine (dAdo) [7].
• Previous work (J. A. Nelson, J. F. Kuttesch, Jr., and B. H. Herbert. Biochemical Pharmacology 32: 2323-2327, 1983) indicated a role for the classic organic cation transporter (OCT) in the secretion of the dAdo analog, 2'-deoxytubercidin, by mouse kidney [8].

Gene context of deoxyadenosine

• When carried out under oxygen-enriched atmosphere, the reaction of HNE with dAdo yielded 1,N6-ethenodeoxyadenosine (1,N6-EdAdo) and 7-(1',2'-dihydroxyheptyl)-1,N6-EdA in 0.03% and 0.48% yield [9].

References