Linear-Quadratic Analysis of Radiosensitization by Halogenated Pyrimidines: I. Radiosensitization of Human Colon Cancer Cells by Iododeoxyuridine

Abstract

As a continuation of the studies in Part I (Miller, Fowler, and Kinsella, Radiat. Res. 131, 000-000, 1992), which examined the radiosensitizing effects of iododeoxyuridine (IdU), similar experiments with bromodeoxyuridine (BrdU) were conducted concurrently to characterize its effects on the shape of the radiation survival curves of cells of two human colon cancer cell lines, HT 29 and HCT 116. The efficiency of radiosensitization by BrdU, expressed as a function of percentage thymidine replacement, was lower when compared to IdU in both cell lines. However, the major radiosensitizing effect of BrdU was manifest as an increase in the initial slope (alpha), just as observed for IdU. However, with BrdU, in contrast to IdU, an increase in curvature (repairable damage) was also evident. Cells of the more radiosensitive line, HCT 116, showed less sensitization by either BrdU or IdU than cells of the more radioresistant line, HT 29. These results were consistent with the proposed mechanism of radiosensitization being an increase in the single-hit character of low-LET radiation. It follows that the radiosensitizing effects of both analogs were largest in the low-dose region of the survival curve.