Effects of the alpha-D-anomer of 5-aza-2'-deoxycytidine on L1210 mouse leukemic cells in vitro and in vivo.
The alpha-D-anomer of 5-aza-2'-deoxycytidine inhibited cell growth in vitro in L1210 mouse leukemic cells (concentration causing 50% inhibition about 1 X 10(-6) M) and was also active in vivo in increasing the life span of mice with L1210 leukemia by 100% after a single i.p. injection (800 to 1000 mg/kg). This effect could be reversed by 2'-deoxycytidine. The alpha-D-anomer produced approximately 100-fold less host toxicity than did 5-aza-2'-deoxycytidine. It was observed that alpha-D-anomer, when kept at 23 degrees for 72 hr, inhibited the uptake of radioactive 2'-deoxycytidine by L1210 cells in vitro as well as the phosphorylation of 2'-deoxycytidine by a cell-free extract from L1210 cells. These effects could not be obtained with the fresh solution of the drug. It is proposed that the action of alpha-D-anomer is due to its conversion to 5-aza-2'-deoxycytidine as shown by high-performance liquid chromatography performed on water solutions of both anomers.
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D000077209:Decitabine; D003842:Deoxycytidine Kinase / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007536:Isomerism; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D014158:Transcription, Genetic / Q000187:drug effects
D000077209:Decitabine; D003842:Deoxycytidine Kinase; D001374:Azacitidine