Reversal of deamination-related cytotoxicity of 5-methyl-2'-deoxycytidine by tetrahydrouridine in human leukemia cells.

Abstract

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.

• Authors: A Jekunen, J A Vilpo
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 73 Issue 5 Pg. 1087-91 (Nov 1984) ISSN: 0027-8874 [Print] United States
• PMID: 6593484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxycytidine
• Tetrahydrouridine
• 5-methyldeoxycytidine
• Uridine

Topics

• Biotransformation
• Cell Line
• Cell Survival (drug effects)
• Deoxycytidine (analogs & derivatives, metabolism, toxicity)
• Humans
• Kinetics
• Neoplasms (metabolism, pathology)
• Tetrahydrouridine (pharmacology)
• Uridine (analogs & derivatives)