5-FLUOROURACIL MODULATION OF RADIOSENSITIVITY IN CULTURED HUMAN CARCINOMA-CELLS

We evaluated conventional pulse exposure versus continuous exposure models of 5-fluorouracil (5-FU) radiosensitization in HT-29 (human colon adenocarcinoma) and DU-145 (human prostate cancer adenocarcinoma) cell lines. Cell survival following treatment with drug and/or radiation was determined by colony formation assays. Radiation was delivered either by itself, approximately midway through a 1-hr exposure to 5-FU (10-mu-g/ml), or at various times following initiation of exposure to 5-FU (0.5-mu-g/ml) present throughout the entire period of incubation. Drug concentrations were selected to approximate those achieved in vivo in humans. HT-29 cells showed a plating efficiency of 87% and similar cytotoxicity (survival reduced to 0.57-0.71) for all 5-FU conditions. The D(o)'s of the radiation survival curves were not different for 1 hr of 5-FU exposure versus radiation alone. However, continuous exposure conditions demonstrated statistically significantly different D(o)'s from radiation alone and pulse 5-FU exposure. DU-145 cells displayed a plating efficiency of 17% and cytotoxicites of 0.10-0.91 for the 5-FU conditions. DU-145 cells showed different radiation-5-FU interactions: 5-FU produced statistically significant changes in D(o) whether administered as a 1-hr pulse or as a continuous exposure. The limitations of this experimental model as well as the differences between cell lines insofar as their radiosensitization by 5-FU underscore the caution required in extrapolating these radiobiologic models to the clinical setting.