Protection of leukemic cells by deoxycytidine: in vitro measures of protection against cytosine arabinoside.
Plasma deoxycytidine levels can be very high in leukemia patients. Such levels strongly protected leukemia cell lines against cytosine arabinoside (araC), fludarabine and 2-chlorodeoxyadenosine when using clonogenic survival as the endpoint. This endpoint is not easily used when studying protection in clinical leukemia cell samples. Therefore, we tested other ways to quantify protection based on biochemical measures of viability or drug metabolism. The estimates of the strength of protection based on rates of DNA synthesis, cellular araC uptake and incorporation of araC into DNA were much lower than the estimates using clonogenic survival. The MTT viability assay gave excellent estimates and appears promising for studying protection in primary leukemia cell samples.
Cohen
J D
JD
University of Colorado Health Sciences Center, Division of Medical Oncology, Denver 80262, USA.
Strock
D J
DJ
LaGuardia
E A
EA
Mao
Z
Z
Teik
J E
JE
D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D003841:Deoxycytidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000473:pathology*; D013778:Tetrazolium Salts / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005562:Formazans; D013778:Tetrazolium Salts; D003561:Cytarabine; D003841:Deoxycytidine; C079782:MTT formazan; D004247:DNA