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• W2145373090 abstract "Several halogenated analogs of thymidine and cytodine are powerful sensitizers of bacterial and mammalian cells to lethal effects of x-irradiation, and as such they are of interest to clinical radiotherapy (1–8). To be effective, these analogs must be incorporated into the newly formed DNA molecule during the S period or time that the DNA molecules of a cell are being replicated. Therefore, cells in G2-G12 phases of the cell cycle, even when such an agent was present in effective concentration, would show no change in radiosensitivity in terms of change in D0 and m3. The analogs of thymidine which have been found to be effective sensitizers are 5 bromo-, iodo-, or chlorodeoxyuridine (BUdR, IUdR, and CUdR); also, bromodeoxycytidine (BCdR) is a potent radiation sensitizer. The magnitude of sensitization is a function of the extent of thymine replacement by the analog. BUdR and BCdR have been reported to reduce the D0 by a factor of 1.5–1.7 (no change in m) at drug concentrations which do not have demonstrable toxic effects on cells (3, 6, 8). At higher but toxic drug doses, the D0 may be reduced by a factor ≈ 2.5 and m reduced to ≈ 1.0. An important factor limiting the effectiveness of such agents in tumor therapy will be the size of the fraction of cells that can be sensitized. For example, to reduce sharply the radiation dose which would yield permanent local control in 90 per cent of treated tumors, the TCD90, virtually 100 per cent of the viable tumor cells must pass through at least one S phase during the time of drug infusion. The probability of sensitizing essentially all the cells would be a function of the distribution of the cell generation times within the tumor cell population. The proportion of viable cells whose G1 periods are longer than the infusion time would limit the change in TCD90 effected by the drug treatment. Kaplan (9) noted that if the repair of sublethal damage by cells in the G1 phase involves synthesis of DNA, then some sensitization of G1 cells exposed to an agent such as 5 BUdR might be observed. Studies on individual HeLa cells cultured in vitro showed that although the mean generation time was eighteen hours, some fifty-two to fifty-seven hours were required for 92–98 per cent of the cells to complete the cell cycle (10). Similar studies on a human amnion cell line showed that the mean generation time was eighteen hours, but that thirty hours were required for 99 per cent of the cells to move through at least one cell cycle (11)." @default.
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• W2145373090 date "1966-12-01" @default.
• W2145373090 modified "2023-09-26" @default.
• W2145373090 title "Theoretical Evaluation of a Limitation in the Use of Pyrimidine Analogs in Radiation Therapy" @default.
• W2145373090 doi "https://doi.org/10.1148/87.6.1065" @default.
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