Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. I. Radiosensitization of human colon cancer cells by iododeoxyuridine.

Radiosensitization by iododeoxyuridine (IdU) is a method of enhancing cell killing in the radiotherapy of human cancers, especially for tumors that proliferate faster than the surrounding normal tissues, such as might appear in brain or liver. We have investigated in vitro the relationship between the amount of thymidine replacement by IdU and the resulting radiosensitization in two human colon cancer cell lines, HCT 116 and HT 29, with differing inherent sensitivities to X rays. The results show that an increase in the initial slope of the cell survival curve was the predominant mode of radiosensitization. In this situation, the emphasis on changes in the initial slope suggest the use of a survival curve model that contains the initial slope as a defined variable, which the traditional single-hit, multitarget model does not. We present our analyses mainly in terms of alpha (initial slope) and changes in surviving fraction at 2 Gy and also as a modified form of sensitizer enhancement ratio that describes the dose-modifying factor of IdU at a single radiation dose of 2 Gy (SER 2 Gy). Iododeoxyuridine is an effective radiosensitizer in both cell lines, but IdU appears especially effective in increasing the initial slope of the more radioresistant line, the HT 29 cells.