Reversal of deamination-related cytotoxicity of 5-methyl-2'-deoxycytidine by tetrahydrouridine in human leukemia cells.
The present experiments were conducted to test the effects of the potent cytidine deaminase inhibitor tetrahydrouridine (THU) on the metabolism and cytotoxicity of 5-methyl-2'-deoxycytidine (5-Med-Cyd) in several human leukemia cell lines in vitro. It was observed that 5-Med-Cyd exerts its effects via deamination to thymidine, which is particularly toxic to human promyelocytic (HL-60) and T-cell (JM) leukemia cell lines in vitro. The deamination and the cytotoxicity of 5-Med-Cyd were effectively hindered by 10(-3) M THU in 3-day cultures of HL-60 cells. Although the catabolism of [14C]5-Med-Cyd in the HL-60 cell cultures was blocked by THU, no radioactive 5-Med-Cyd was incorporated into DNA. The cytotoxicity and DNA incorporation of fluorodeoxycytidine are enhanced by THU. Unlike that compound 5-Med-Cyd resembled more bromodeoxycytidine and iododeoxycytidine; THU decreases the toxicity of both of these deoxycytidine analogues.[1]References
- Reversal of deamination-related cytotoxicity of 5-methyl-2'-deoxycytidine by tetrahydrouridine in human leukemia cells. Jekunen, A., Vilpo, J.A. J. Natl. Cancer Inst. (1984) [Pubmed]
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