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- W2079080667 abstract "1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC) and 5,6-dihydro-5-azacytidine (DHAC) are two new antitumor agents under clinical investigations, which exhibit the chemical similarities found in the tumoricidal drug cytosine arabinoside (ara-C) and the nitrogen substitution in the 5 position of the pyrimidine ring found in 5-azacytidine (5-aza-C). The cellular anabolism of ara-AC and DHAC and their effect on DNA methylation have been examined in two new human leukemia cell lines, which are sensitive (PER-145) and resistant (PER-163) to ara-C. The triphos-phate anabolite of ara-AC, ara-ACTP, was the major cellular anabolite in the cellular extracts of the PER-145 cells, reaching a cellular saturation concentration of 64.1 +/- 3.2 microM using 25 microM of the drug. Only trace levels of ara-ACTP were detected in the PER-163 cell line, which lacks deoxycytidine kinase, after exposure to a similar concentration. Notably, after 1 mM, the ara-ACTP concentration averaged 12 +/- 3 microM. DHAC was anabolized by both cell lines to a similar degree but required much higher nucleoside concentrations (100 microM or higher) to achieve similar cellular concentrations of its triphosphate, DHACTP. Although the deoxy-derivative, DHAdCTP, was detected in both cell lines, it was detected at 1-2 log10 lower concentrations than DHACTP. DNA methylation studies showed that DHAC had a profound effect in inducing DNA hypomethylation in both cell lines, with nadir values of 27.3 and 29.2% of control.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
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- W2079080667 date "1995-04-01" @default.
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- W2079080667 title "Biochemical pharmacology and DNA methylation studies of arabinosyl 5-azacytidine and 5,6-dihydro-5-azacytidine in two human leukemia cell lines PER-145 and PER-163" @default.
- W2079080667 doi "https://doi.org/10.1097/00001813-199504000-00015" @default.
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