Inhibition of recovery from damage induced by ionizing radiation in mammalian cells.
Recent studies indicate the importance for radiotherapy of the inherent radiosensitivity of tumour cells in the low-dose region; a region where recovery is probably almost complete. Improvements in radiotherapy may therefore depend on the search for specific inhibitors of cellular recovery. This review summarizes data from studies in which use was made of a variety of mammalian, including human cell systems, where attempts have been made to inhibit recovery using chemical agents. Inhibition of sublethal damage repair, potentially lethal damage repair and low dose-rate sparing has been observed to varying extents by several agents including those thought to act by interfering with DNA repair processes (e.g. ara-C, 3-aminobenzamide) differentiation-inducing agents (e.g. N-methylformamide), halogenated pyrimidines (e.g. iododeoxyuridine), caffeine and chemotherapeutic agents (e.g. adriamycin). No individual agent stands out as exerting an exceptionally dramatic effect on recovery. However, of the agents used clinically, cis-platinum appears to hold some promise, while iododeoxyuridine, N-methylformamide, beta ara-A and caffeine all appear to inhibit to some extent the recovery of ionizing radiation-induced damage. There is an urgent need for further study to determine, in particular, relative effects in tumour versus normal cell types and whether any agents found to be effective in vitro show similar effects in vivo.
Kelland
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LR
Radiotherapy research Unit, Institute of Cancer Research, Sutton, Surrey, U.K.
Steel
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D005978:Glutathione / Q000502:physiology; D066298:In Vitro Techniques; D011743:Pyrimidines / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011743:Pyrimidines; D012997:Solvents; D002110:Caffeine; D005978:Glutathione