Modification of radiosensitivity and recovery from X ray damage in vitro by retinoic acid

We studied the effects of all-trans retinoic acid (RA) combined with X-irradiation on confluent cultures of human breast cancer (MCF-7) and melanoma (C-143) cell lines, as well as in a normal human diploid fibroblast strain (AG 1522). RA in non-cytotoxic concentrations was a potent inhibitor of confluent holding recovery of potentially lethal damage (PLD repair) for all three cell types. A complete inhibition of recovery was observed at lower RA concentrations in the tumor lines than in the fibroblast strain. Exposure to RA prior to and during irradiation resulted in a radiosensitizing effect that was similar in MCF-7 and AG 1522 cells. The implications of these findings are discussed in terms of the potential value of retinoids as biological response modifiers for the clinical radiotherapy of cancer.