The independent action of radiation and cisplatin on the survival or recovery of human normal or tumour cells in vitro or in vivo.
Recovery from radiation- or cisplatin-induced lethal damage has been studied in euoxic normal human foetal lung fibroblasts (HFL cells) that remain viable for at least 20 days in plateau-phase culture. After a 1 hour treatment with cisplatin the half-time of recovery was about 2 days. By contrast recovery after radiation was more rapid with half-times of approximately 10 h. There was no further measurable recovery after 2 days. With either agent the recovery ratios (RR) were dose-dependent but recovery (following treatment with equitoxic doses of the two agents) was appreciably greater after cisplatin (RR approximately 123 after 40 microM for 1 h) than after radiation (RR approximately 15 after 900 cGy). When radiation (900 cGy) was combined with cisplatin (40 microM for 1 h) the cell survival, measured at 5 days or later times after the treatments, was not significantly less than that predicted by the additive, independent effects of both agents (calculated as the product of their respective effects on cell survival) irrespective of whether cisplatin was given 1 h before, during or for 1 h immediately after radiation. In euoxic, exponentially growing HFL or HeLa cells there was no evidence that combinations of cisplatin and radiation gave more than additive toxic effects in the protocols tested. The combined effects of cisplatin or carboplatin and whole-body irradiation given 45 min later, on human melanoma cells (assessed by their colony-forming abilities in vitro) growing in thymectomised mice, were essentially the same as that predicted by the additive, independent effects of the two agents.
Basham
C
C
Molecular Pharmacology Unit, Institute of Cancer Research, Sutton, Surrey, U.K.
Mills
J
J
Douple
E B
EB
Roberts
J J
JJ
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects*; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D002945:Cisplatin