Detail of "1927-31-7"

Reference

Effect of 9-

Effect of 9-.beta.-D-arabinofuranosyladenine on DNA synthesis in vivo. Mueller, Werner E. G.; Maidhof, Armin; Zahn, Rudolf K.; Shannon, William M. (Inst. Physiol. Chem., Univ. Mainz, Mainz, Ger.). Cancer Res., 37(7, Pt. 1), 2282-90 (English) 1977. CODEN: CNREA8. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) The influence of 9-.beta.-D-arabinofuranosyladenine (I) [5536-17-4] on DNA synthesis in an intact cell system was studied, using mouse lymphoma cells (L5178Y) in suspension culture. These cells are characterized by the low adenosine deaminase level of 23 enzyme units/108 cells. In synchronized cells, the deoxyadenosine 5'-triphosphate (dATP) [1927-31-7] pool increased from 1.3 pmols/106 cells during G1 phase to 4 pmols/106 cells during S phase. I was intracellularly heavily phosphorylated to 9-.beta.-D-arabinofuranosyladenine 5'-triphosphate (ara-ATP) [3714-60-1]; 61% of the total I uptake was present as ara-ATP; the pool size of ara-ATP was approx. 1 pmol/106 cells. The DNA polymerase [9012-90-2] .beta. activity increased 4-fold during transition from G1 to S phase, whereas the .beta. enzyme remained const. The RNA polymerase I and II activity changed only slightly during G1 and S phase. These parameters, all of which were capable of influencing DNA synthesis, were not altered in amt. during incubation of the cells with I concns. capable of inhibiting cellular DNA synthesis almost completely. When the intracellular dATP pool size was increased, the potency of I in inhibiting cell proliferation diminished. Apparently, the I-caused decrease of cell proliferation is a consequence of a competitive inhibition of DNA polymerase .alpha. by ara-ATP. This conclusion is also supported by a calcn. using the Michaelis const. for dATP and the inhibitor const. for ara-ATP of DNA polymerase .alpha., as well as by the intracellular dATP and ara-ATP pool sizes. By a double I block, an unsynchronized cell population can be synchronized to 62%.

Deoxyadenosine metabolism and toxicity in cultured L5178Y

Deoxyadenosine metabolism and toxicity in cultured L5178Y. Lowe, Jeffrey K.; Gowans, Bonnie; Brox, Larry (Cancer Res. Unit, Univ. Alberta, Edmonton, Alberta, Can.). Cancer Res., 37(9), 3013-17 (English) 1977. CODEN: CNREA8. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) The growth of cultured L5178Y cells was inhibited by relatively low concns. of deoxyadenosine (I) [958-09-8] in the presence of deoxycoformycin, an inhibitor of adenosine deaminase [9026-93-1]. Cell viability was reduced, presumably as a consequence of the induced state of unbalanced growth which is characterized by inhibition in DNA synthesis, accumulation of cells in G1 or early S phase, a continuation in RNA synthesis, and increasing cell vol. The intracellular concns. of purine and pyrimidine ribonucleoside phosphates remained essentially unchanged. The significant changes in the intracellular deoxynucleoside triphosphate pools were an increase in deoxyadenosine triphosphate [1927-31-7] and a decrease in deoxycytidine triphosphate [2056-98-6].