Reference

2-Fluoroadenosine 3',5'-monophosphate

2-Fluoroadenosine 3',5'-monophosphate. A metabolite of 2-fluoroadenosine in mouse cytotoxic lymphocytes. Zimmerman, Thomas P.; Rideout, Janet L.; Wolberg, Gerald; Duncan, Gail S.; Elion, Gertrude B. (Dep. Exp. Ther., Wellcome Res. Lab., Research Triangle Park, N. C., USA). J. Biol. Chem., 251(21), 6757-66 (English) 1976. CODEN: JBCHA3. DOCUMENT TYPE: Journal CA Section: 3 (Biochemical Interactions) 2-Fluoroadenosine (I) [146-78-1] is a potent inhibitor of lymphocyte-mediated cytolysis studied in vitro. The inhibition of cytolysis by I was potentiated markedly by Ro 20-1724, an inhibitor of adenosine 3':5'-monophosphate (cAMP) phosphodiesterase and, unlike the inhibition caused by adenosine, was irreversible when the cytotoxic lymphocytes were incubated with I and were then washed free of exogenous nucleoside. Incubation of cytotoxic lymphocytes with I resulted in the rapid, dose-dependent formation of 2-fluoroadenosine 5'-triphosphate (II) [1492-62-2]; the build-up of II within these cells was accompained by a reciprocal depletion of ATP. Once formed intracellularly, the II was not diminished during a subsequent 30-min incubation of the cells in I-free medium. 2-Fluoroadenosine 3':5'-monophosphate (III) [61423-58-3], a novel compd., was found to be highly cross-reactive in a radioimmunoassay specific for cAMP and to be equipotent to cAMP in its ability to activate a crude prepn. of protein kinase derived from rat brain. Treatment of cytotoxic lymphocytes with I resulted in the formation of presumptive III in amts. greater than that of cAMP, as detd. by radioimmunoassay. The cellular formation of the putative III was dependent both on time and on the concn. 61423-58-3 and 1492-62-2 which are cas registry numbers of chemicals are mentioned. of I added to the medium and was not obsd. when the lymphocytes were incubated with either adenosine or 2-chloroadenosine, 2 agents which caused large increases in cAMP. The simultaneous presence of Ro 20-1724 enhanced greatly the formation of III from I without affecting the pool size of II. Removal of exogenous I from cells previously incubated with this drug and subsequent incubation of these cells in drug-free medium did not result in a substantial redn. in intracellular III. Adenosine caused a marked elevation of III in lymphocytes which had been preloaded in this capacity, while 9-.beta.-D-arabinofuranosyladenine was without effect. The level of cAMP was elevated transiently, in a dose-dependent manner, by I, and returned to control value after of exogenous I from the cells. Ro 20-1724 enhanced greatly this transient elevation of cAMP caused by I. .

Kinetics of reduction in viability of cultured leukemia L1210 cells exposed to purine analogs

Kinetics of reduction in viability of cultured leukemia L1210 cells exposed to purine analogs. Wilkoff, Lee J.; Dulmadge, Elizabeth A.; Lloyd, Harris H. (Kettering-Meyer Lab., South. Res. Inst., Birmingham, Ala., USA). Chemotherapy (Basel), 23(3), 179-91 (English) 1977. CODEN: CHTHBK. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Rates of decrease in viability and degree of cell killing were relatively independent ofconcns. when replicating cultured L1210 cells were exposed to increasing concns. of 6-thioguanine (I) [154-42-7], 6-methylthiopurine ribonucleoside [342-69-8], 9-.beta.-D-arabinofuranosyl-9H-purine-6-thiol [892-49-9], or 9-ethyl-6-thiopurine [17416-85-2]. The realtive lack of dependence of cell killing rate on cytotoxic concns. suggest (a) that these agents may be only effective against proliferating cells, and (b) that only limited therapeutic advantage can be gained by increasing their concn. beyond a min. effective level. In contrast, the rate and degree of cell killing were dependent upon concns. when cells were exposed to increasing amts. of 4-aminopyrrolo[2,3-d]pyrimidine bD- ribofuranoside (II) [69-33-0] or 2-fluoroadenosine [146-78-1], indicating that these analogs are not cell-cycle-stage-sp. and that nonreplicating cell populaions may be sensitive to them.