Reversible suppression of malignancy and differentiation of melanoma cells.

Tumorigenicity is reversibly suppressed in mouse melanoma cells grown with 5-bromodeoxyuridine (BrdU). The nontumorigenic cells are immunogenic, and preinjection of these cells can protect mice against tumors inevitably formed when the parental, untreated melanoma cells are inoculated into inbred strain C57BL/6. A mixture of highly immunogenic clone, C(3)471, with malignant cells is also nontumorigenic. These effects are related to the host immune response since they occur only in immunocompetent mice. BrdU also reversibly suppresses functions related to pigment formation and plasminogen activation. These effects require incorporation of BrdU into DNA, emphasizing the value of the thymidine analog, BrdU as a tool to relate normal regulation of gene activity to perturbations of this regulation which produce malignant cells. This research can facilitate basic understanding of the malignant state and its relationship to host response as well as a method for immunizing melanoma patients after surgery to prevent tumor recurrence.