RESPONSE OF PRIMARY COLON-CANCER CELLS IN HYBRID SPHEROIDS TO 5-FLUOROURACIL

We have measured the clonogenic survival of cells isolated directly fr om colon cancer surgical specimens and treated with 5-fluorouracil (5- FU). Enzymatically disassociated cells were incorporated into hybrid s pheroids, consisting predominantly of nonproliferating HeLa feeder cel ls. Aliquots were exposed for 1.5 hr to a range of concentrations of 5 -FU. From the decrease in clonogenic survival, as deduced from the fre quency of colony formers among hybrid spheroids after chemical treatme nt, we were able to construct survival curves in 50% of the surgical s pecimens tested. A striking revelation was the presence of a resistant plateau in the survival curves, reminiscent of the solid tumor respon se to treatment with 5-FU. This resistance was absent in monolayer cul tures. Evidence is presented that this resistance is due to the absenc e of, or delay in, cell cycle progression of cells residing in hybrid spheroids.