DEOXYCYTIDINE IN HUMAN PLASMA - POTENTIAL FOR PROTECTING LEUKEMIC-CELLS DURING CHEMOTHERAPY

Degradation of DNA produces deoxycytidine. Metabolism of deoxycytidine to dCTP inhibits phosphorylation of cytosine arabinoside (araC), flud arabine (FaraA) and 2-chlorodeoxyadenosine (CdA) by deoxycytidine kina se. This study measured plasma deoxycytidine in healthy adults and two leukemia patients and then determined how clinically relevant deoxycy tidine levels would affect drug toxicity in human leukemia and lymphom a cells. Deoxycytidine was well below 0.05 mu M in ten healthy persons . In the leukemia patients it was <0.05 and 0.44 mu M before chemother apy, rising to 10.3 and 5.5 mu M during treatment. A broad range of cl inically relevant deoxycytidine levels were high enough to profoundly decrease araC, FaraA and CdA toxicity in MOLT3, CA46 and HL60 leukemia /lymphoma cells and to change dCTP, DNA synthesis and drug incorporati on into DNA in a manner consistent with prior mechanistic studies. Var ying deoxycytidine levels could be an important factor influencing leu kemia therapy. (C) 1997 Elsevier Science Ireland Ltd.