Radiosensitization of Nonhypoxic Cells by Halogenated Pyrimidines
Halogenated pyrimidine analogs such as iododeoxyuridine (IdUrd) have been recognized as potential clinical radiosensitizers for over two decades (Djordjevic and Szybalski 1960; Erik- son and Szybalski 1963; Kaplan and Tomlin 1960; Kinsella et al. 1984a). More recently, in vitro studies suggest these analogs may sensitize certain chemotherapy agents such as bleomycin and cisplatinum (Russo et al. 1986; Ackland et al. 1988), although the mechanism(s) of chemosensitization, like those of radiosensitization, are not clearly understood. However, incorporation into DNA is felt to be necessary for both types of sensitization (Ackland et al. 1988; Kinsella et al. 1987). IdUrd has been shown to be as effective a clinical radiosensitizer as bromodeoxyuridine (BrdUrd), with less systemic skin toxicity (Kinsella et al. 1985; Kinsella et al. 1984b). This skin toxicity is felt to result from photosensitization with fluorescent light and sunlight (Mitchell et al. 1984). Several clinical trials of IdUrd as a radiosensitizer show encouraging results and will be summarized later. Clinical testing of IdUrd as a chemosensitizer with bleomycin is underway as a phase I study sponsored by NCl (R. Schilsky, personal communication, 1990).
KeywordsThymidine Kinase Radio Sensitizer Human Bladder Carcinoma Cell Line Fluorodeoxyuridine Monophosphate Thymidine Triphosphate
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