Effect of Halogenated Pyrimidines on Radiosensitivity of E. coli

Abstract

The incorporation of halogenated thymine and thymidine analogs into Escherichia coli DNA during log-phase growth, though relatively nontoxic, was associated with a significant increase in sensitivity of the bacterial cells to X-ray and UV irradiation. Although incorporation was linear with time from 2 to 10 hours of incubation, significant radiosensitization was not observed until 4 hours (17% replacement of thymine by 5-bromouracil) and was maximal at the end of log-phase growth (40 to 50% replacement), despite a further increment of incorporation during stationary phase. In contrast to other reports in which mammalian cell cultures were employed, labeling of only one strand of the DNA double helix was sufficient to confer at least half- maximal radiosensitization. The implications of these data for clinical radiotherapy are discussed.