REVERSIBLE CHANGES IN RADIATION RESPONSE INDUCED BY ALL-TRANS-RETINOIC ACID

Purpose: The aim was to establish a model of reversible radiosensitization in human tumor cell lines by all-trans retinoic acid without influencing cell cycle or differentiation. Methods and Materials: Three human carcinoma cell lines (one bladder and two lung lines) were incubated in medium containing delipidized serum with or without varying concentrations of all-trans retinoic acid for a range of time periods, and their acute response to radiation measured by clonogenic assay, Cell phenotype was monitored using growth rates, morphology, and intermediate filament expression. Results: Two of the three cell lines (those in which cell kill was predominantly through reparable damage beta in control cultures) showed an increase in radiosensitivity with retinoic acid, at a concentration with no discernable effect on phenotype (10(-7) M). No significant change in cu values was observed, The values for beta increased from 0.057 to 0.109 and from 0.039 to 0.075, corresponding to dose modification factors of 1.59 and 1.67, When retinoic acid was removed prior to irradiation, cell survival returned to control levels by 48 h. Conclusion: Radiosensitization occurred at retinoic acid concentrations that did not otherwise perturb the cells; the effect may be due to inhibition of DNA repair in cells usually competent at repair, The model provides a method of altering radiosensitivity in selected cell lines without genetic mutation, which may enable investigation of DNA repair mechanisms.