Sequencing radiation and adriamycin exposures in spheroids to maximize therapeutic gain

Chinese hamster V79 spheroids were used as a tumor model to investigate sequence effects for combination treatments with adriamycin and radiation. Using cell sorting techniques, the subpopulation of cells most resistant to each modality as a single agent was identified, and combination treatments were then evaluated with the intent of identifying protocols leading to enhanced efficacy against the cell subpopulations that normally limited the success of single-agent treatments. Pre-irradiation drug exposure had the greatest therapeutic potential, not due to drug/radiation interactions, but rather, to drug-induced spheroid reoxygenation. Conversely, post-irradiation drug exposure was judged to have little potential for therapeutic gain, since the same cell subpopulations were killed (or spared) by the two agents.