Application of non-hypoxic cell sensitizers in radiobiology and radiotherapy: rationale and future prospects.
The effects of commonly used non-hypoxic cell radiosensitizers are briefly reviewed. Emphasis is placed on the effects and the mechanism of action of halogenated pyrimidines, since recent clinical trials indicated the potential importance of these compounds in the treatment of certain types of human tumors. Evidence is presented suggesting that halogenated pyrimidines sensitize cells to radiation by increasing induction of DNA and chromosome damage per cell per unit absorbed dose, as well as by increasing the susceptibility to fixation of radiation induced PLD. The former mode of action correlates with an increase in survival curve slope, whereas the latter probably causes the reduction observed in shoulder width. The effects of repair inhibitors such as the nucleoside analogs are briefly reviewed and their possible clinical importance discussed. Results are presented indicating that combined treatment with halogenated pyrimidines and nucleoside analogs may enhance the radiosensitizing effect of the former and the specificity on tumor cells of the latter. Finally, the effects of other radiation sensitizers such as 3-aminobenzamide and diamide are briefly summarized.
Iliakis
G
G
Thomas Jefferson University, Department of Radiation Oncology and Nuclear Medicine, Philadelphia, PA 19107.
Kurtzman
S
S
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects; D003958:Diamide / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009705:Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D001391:Azo Compounds; D001549:Benzamides; D009705:Nucleosides; D011838:Radiation-Sensitizing Agents; D003958:Diamide; D010100:Oxygen