Flow microfluorimetric analysis of sensitive and resistant leukemia L1210 following 1-beta-D-arabinofuranosylcytosine in vivo.

Two groups of BALB/c X DBA/S F1 mice with sensitive and 1-beta-D-arabinofuranosylcytosine-resistant L1210 ascites, respectively, were used to study the cytokinetic effects of a single dose of 750 mg of 1-beta-D-arabinofuranosylcytosine per kg. Sequential DNA histograms, labeling indices, and mitotic indices were obtained from each of five mice at timed intervals from 0 to 72 hr. Each histogram was obtained by flow microfluorimetry, using the DNA-specific fluorochrome, mithramycin. The histograms were then integrated for cell cycle analysis. Cytokinetic perturbations occurred in both groups, but they were greater in the sensitive population where there was a relative accumulation of cells, mainly in early S phase, at 16 hr. This was followed by a relative depletion of S-phase cells. In the resistant population, there were relative accumulation of cells in early S phase at 8 and 24 hr and in mid-S phase at 32 hr, but there was no subsequent relative depletion of S-phase cells. The labeling index was rapidly reduced in both groups but was recovered in the resistant population within 4 hr. In the sensitive population, there was a transient rise in the labeling index at 8 and 16 hr. Sensitive and resistant populations of L1210 cells were rapidly and reliably distinguished by DNA content cell cycle analysis of a single sample taken between 24 and 72 hr following a large dose of 1-beta-D-arabinofuranosylcytosine. This technique has potential clinical application in the rational design and monitoring of chemotherapy.