The treatment of tumor cells in culture with chloroquine after irradiation significantly reduces their survival, but no enhancement is seen when the cells are treated with the drug before irradiation. This suggests that the potentiation of the radiation response by chloroquine results from the impairment of the post-irradiation recovery processes. Incorporation studies with melanotic melanoma cells in culture derived from human malignant melanoma demonstrate significantly higher uptake of the compound than in amelanotic melanoma, HeLa, or nonpigmented human diploid cells in culture. The significance of these findings is discussed in relation to the potential use of the drug as a radiosensitizer in selected human tumors.
N THE ABSENCE OF SIGNIFICANT INTRINSIC
I differential radiosensitivity between most of malignant cells and the surrounding normal cells, attempts have been made to improve the therapeutic index (the ratio of the normal tissue tolerance dose to the tumor lethal dose) by other means. Two such methods are modification of the radiation response of the target tissue with chemicals or, if the tumor cells are partially anoxic, the use of radiation of high linear energy transfer (LET). An optimum means for chemical modification of the radiation effects in clinical radiotherapy would be the use of a nontoxic compound that would be preferentially incorporated into the tumor cells and that would potentiate the lethal effects of radiation, thus enhancing the radiation effects in the irradiated tumor relative to normal cells.