A comparison of clonogenic and radionuclide uptake assays for determining the radiation response of human small-cell lung cancer xenografts and cell lines.

Abstract

Previous work has suggested that a radionuclide (3HTdR) uptake assay can provide a measure of drug and radiation sensitivity comparable with that given by the clonogenic assay. We have now extended this work to examine the radiation response of human small-cell lung cancer xenografts and cell lines with a wide range of plating efficiencies. Preliminary experiments using cultured cells indicated that irradiation of a single-cell suspension following disaggregation generally produced similar response data to those obtained when cultures were irradiated in situ and subsequently disaggregated. The response of eight cell lines to a single dose of 2 Gy was measured using both radionuclide uptake and clonogenic assays. There was no correlation between the two sets of data. Agreement between the radiation-response curves obtained using 3HTdR uptake and clonogenic assays was better for high plating efficiency xenografts (NCI-H69, COR-L51) than for low plating efficiency xenografts (COR-L24, COR-L31). Radionuclide uptake indicated very shallow response curves for the low plating efficiency lines. Altering the time of radionuclide addition from the standard Day 4 to other times between Day 2 and Day 6 did not greatly change the indications of radioresponsiveness provided by the assay. Growth-curve experiments for line COR-L24 showed that cell numbers at Day 4 after irradiation with 1.5 Gy or 3 Gy were very similar to those in unirradiated cultures. For NCI-H69, however, the cell numbers were very different for the different radiation doses. It appears that a high proportion of cells in lines such as COR-L24 take many days to show radiation damage as measured by reduced 3HTdR uptake.