Differential response of cultured human normal and tumor cells to trace element-induced resistance to the alkylating agent melphalan

Previous studies using cultured Chinese hamster cells indicated that pretreatment of the cells with the trace elements copper, selenium, and/or zinc resulted in increased survival of the metal-induced cultures following subsequent exposure to mono- and bifunctional alkylating agents. To ascertain whether a comparable protective response could be activated in human-derived material, a series of human normal and tumor cells was treated with these trace elements and later challenged with the alkylating agent melphalan, prior to determination of the surviving fraction via colony formation. Normal human cells derived from either newborn infants or adults exhibited an increase in survival of 7- to 9-fold when pretreated with zinc alone that increased to approximately 16-fold when these normal cells were induced with all three trace elements. In contrast, comparable pretreatment of tumor cell populations resulted in an increase in survival of 1.7-fold or less, with most types of tumors exhibiting no induced protection. These observations describing a differential inducibility of normal and tumor cells raise the possibility of a novel approach for selectively sparing normal tissue in patients undergoing treatment with alkylating agents. Possible ramifications to cancer chemotherapy are discussed.