5-Methyl-2'-deoxycytidine. Metabolism and effects on cell lethality studied with human leukemic cells in vitro.
5-Methylcytosine ( 5MeCyt ) is a possible regulator of eukaryotic gene transcription. We investigated whether this compound could be introduced into DNA from exogenous deoxyribonucleoside 5-methyl-2'-deoxycytidine ( 5MedCyd ). High concentrations of 5MedCyd inhibited the growth of several types of human leukemic cell lines in vitro. However, the effect could be accounted for by dThd, a deamination product of 5MedCyd . We found that radioactivity from [methyl-14C] 5MedCyd and [2-14C] 5MedCyd was incorporated into DNA as thymidylate, and none was present as 5MeCyt . There are two conceivable metabolic pathways from 5MedCyd to thymidylate. The first consists of deoxycytidine or thymidine kinase and deoxycytidylate deaminase, and the second of sequential reactions catalyzed by deoxycytidine deaminase and thymidine kinase. No indication of the first pathway was demonstrable in human leukemic cells. We conclude that the DNA exclusion of 5MeCyt from exogenous 5MedCyd takes place because of powerful deoxycytidine deaminase activity in human malignant hematopoietic cells.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D003853:Deoxyribonucleosides / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000503:physiopathology*; D007945:Leukemia, Lymphoid / Q000503:physiopathology
D003853:Deoxyribonucleosides; D003841:Deoxycytidine; C016569:5-methyldeoxycytidine