Biomedical subjects

L J Folstad

Publications and source records attributed to L J Folstad.

2 recordsLinked to original sources

PubMed1982

Quantitative analysis of the cytokinetic response of KHT tumors in vivo to 1-beta-D-arabinofuranosylcytosine.

Quantitative estimates of cytokinetic perturbations induced over a 30-hr interval in KHT tumor cells in vivo by a single dose of 1-beta-D-arabinofuranosylcytosine (ara-C) were inferred from measurements of DNA distribution sequences, tritiated thymidine incorporation into tumor cell DNA, and radioactivity of cells labeled with tritiated thymidine prior to treatment with ara-C. These data were analyzed collectively to produce a mathematical model describing the effects of ara-C on tumor cell cycle kinetics. During analysis, we postulated that ara-C produced a transient block at the a G1-S-phase boundary, that ara-C killed all cells in S phase, and that the cells killed by ara-C did not cycle after treatment. The analysis showed that the duration of the G1-S-boundary block was 5.5 hr, that cells were recruited from G0 into cycle beginning 5.5 hr posttreatment, and that the G1, S, and G2M phase durations of the clonogenic cells which were initially 2, 11.5, and 2 hr, respectively, changed to 0.8, 4.6, and 0.8 hr at 14 hr posttreatment. Cells killed by ara-C were removed from the tumor beginning 10 hr posttreatment. We then used the mathematical model to predict clonogenic tumor cell survival following a second dose of ara-C administered at time intervals ranging from 1 to 30 hr after the first treatment. Clonogenic tumor cell survival following the second dose of ara-C was then experimentally determined and agreed well with the model predictions.

Animals↗

PubMed1981

Solid KHT tumor dispersal for flow cytometric cell kinetic analysis.

We used a bacterial neutral protease to disperse KHT solid tumors into single cell suspensions suitable for routine cell kinetic analysis by flow cytometry and for clonogenic cell survival. Neutral protease disaggregation under conditions which would be suitable for routine tumor dispersal was compared with a trypsin/DNase procedure. Cell yield, clonogenic cell survival, DNA distributions of untreated and drug-perturbed tumors, rates of radioactive precursor incorporation during the cell cycle, and preferential cell cycle phase-specific cell loss were investigated. Tumors dispersed with neutral protease yielded approximately four times more cells than those dispersed with trypsin/DNase and approximately a 1.5-fold higher plating efficiency in a semisolid agar system. Quantitative analysis of DNA distributions obtained from untreated and cytosine-arabinoside-perturbed tumors produced similar results with both dispersal procedures. The rates of incorporation of tritiated thymidine during the cell cycle were also similar with neutral protease and trypsin/DNase dispersal. Preferential phase-specific cell loss was not observed with either technique. We find that neutral protease provides good single cell suspensions of the KHT tumor for cell survival measurements and for cell kinetic analysis of drug-induced perturbations by flow cytometry. In addition, the high cell yields facilitate electronic cell sorting where large numbers of cells are often required.

Animals↗