Characteristics of mouse leukemic cells resistant to 5-azacytidine and 5-aza-2'-deoxycytidine.

Abstract

Summary During the development of resistance to 5-azacytidine, AKR mouse leukemic cells incorporated significantly less cytidine and 5-azacytidine into nucleic acids than their wild-type counterparts. At the same time, 5-aza-2′-deoxycytidine-resistant mutant cells showed a decline in the uptake of 2′-deoxycytidine. This impairment was closely associated with the gradual development of resistance in both cases. Whereas 5-azacytidine inhibited the synthesis of pyrimidines de novo and the hormonal induction of tryptophan pyrrolase, no similar effect was observed with its 2′-deoxyderivative. Leukemic cells resistant to 5-aza-2′-deoxycytidine retained their sensitivity toward 5-azacytidine almost completely. In contrast, their 5-azacytidine-resistant counterparts were practically cross-resistant to 5-aza-2′-deoxycytidine.