Retinoic acid inhibits the fixation of initial transformational damage in X-irradiated Balb/3T3 mouse fibroblasts in vitro.

We have examined the effects of all-trans retinoic acid (RA) on confluent holding recovery (cell survival) and on the fixation of initial transformational damage expressed as the ultimate yield of transformed foci following X-irradiation of density-inhibited cultures of Balb/3T3 cells. Non-cytotoxic concentrations of RA suppressed both recovery of potentially lethal damage and neoplastic transformation in a dose-dependent manner when added for 24 h during post-irradiation confluent holding after a dose of 5 Gy. At 100 microM, RA inhibited the fixation of initial transformational damage by 80%. These findings are discussed in terms of the hypothesis that retinoids may allow a selective enhancement of the inactivation of certain irradiated tumor cells in vivo while reducing the risk of secondary malignancies in successfully treated patients.