Enhancement of mammalian cell killing by 5-fluorouracil in combination with X-rays

The enhanced cytocidal effect of a combination of X-rays and 5-fluorouracil was investigated by means of colony-forming ability in mouse L-cells. Cells were treated with 5-fluorouracil immediately preceding (preirradiation treatment) or following (postirradiation treatment) irradiation. In either pre- or postirradiation treatment with various concentrations of the drug for a fixed time, the enhanced effect was augmented with increasing concentrations of 5-fluorouracil up to 20 microgram/ml. When cells were subjected to postirradiation treatment with a fixed concentration of drug for varying times, the cytocidal effect was further enhanced with increasing duration of drug treatment. In preirradiation treatment, however, drug treatment for longer than 3 hr did not exhibit any further enhancement. Postirradiation treatment with 5-fluorouracil to synchronous cells at various ages demonstrated enhancement at all ages during the cell cycle. The greatest enhancement was observed in the DNA-synthetic phase. Postirradiation treatment with 5-fluorouracil (2.5 microgram/ml) for 24 hr markedly reduced the width of the shoulder of the X-ray survival curve without significantly altering the slope of the exponential portion of the curve. Recovery from sublethal radiation damage was not suppressed by 5-fluorouracil when cells were treated with drug between fractionated X-ray doses. These results indicate that damages caused by 5-fluorouracil and X-rays interact additively to induce cell killing.