Duration of the Dormant State in an Established Cell Line of Human Hematopoietic Cells

Continuous [³H]thymidine labeling and drug sterilization experiments were conducted to determine the duration of the dormant state in an established human hematopoietic cell line (SK-L7) during exponential growth. When growing at their maximum rate, SK-L7 cells have a doubling time of 15 hr, and the majority of cells have unlimited proliferative potential. The continuous labeling experiments showed that 1.64 and 0.08% of the population failed to initiate DNA synthesis in 24 and 96 hr, respectively, and it was estimated that 54 days would be required to label 5 x 10¹²cells. Drugs that are lethal to dormant cells sterilized the population with in 1 hr. Low concentrations of 1-β-D-arabinofuranosylcytosine (ara-C) and hydroxyurea slowed growth but were not lethal, whereas higher concentrations effectively arrested cells in S phase. Some cells recovered after exposure to ara-C for short periods (i.e., 24 hr), but following longer exposure there was little recovery, and the apparent cell kill was greater than would be expected from the labeling data. Cells surviving prolonged treatment with ara-C or hydroxyurea showed little evidence of resistance. The estimated time required to sterilize 5 x 10¹²SK-L7 cells with 10^-5M ara-C was 18 days. These results are compared to published results of similar experiments in L1210 murine leukemia, and the findings are discussed in relation to the estimated duration of treatment with S phase-specific drugs required to eradicate a human leukemic population of 5 x 10¹²cells.