PROTECTION OF LEUKEMIC-CELLS BY DEOXYCYTIDINE - IN-VITRO MEASURES OF PROTECTION AGAINST CYTOSINE-ARABINOSIDE

Plasma deoxycytidine levels can be very high in leukemia patients. Suc h levels strongly protected leukemia cell lines against cytosine arabi noside (araC), fludarabine and 2-chlorodeoxyadenosine when using clono genic survival as the endpoint. This endpoint is not easily used when studying protection in clinical leukemia cell samples. Therefore, we t ested other ways to quantify protection based on biochemical measures of viability or drug metabolism. The estimates of the strength of prot ection based on rates of DNA synthesis, cellular araC uptake and incor poration of araC into DNA were much lower than the estimates using clo nogenic survival. The MTT viability assay gave excellent estimates and appears promising for studying protection in primary leukemia cell sa mples. (C) 1998 Elsevier Science Ltd.