Suppression of malignancy and differentiation in melanotic melanoma cells.

Tumorigenicity of mouse melanoma cells is reduced or lost upon growth in vitro in 1 to 3 mug/ml of 5-bromodeoxyuridine (BUdR). The rate of growth is very little affected by these concentrations. The morphology of the cells is altered, such that the cells grow in a flattened, often fibroblastic monolayer, showing contact inhibition, instead of the rounded, multilayered mounds characteristic of the line. Melanotic cells lose their pigment-producing ability within one week. These effects are reversible and the inclusion of thymidine with BUdR prevents their occurrence. The reduction in tumorigenicity, the effects on cell morphology, and the suppression of pigmentation occur in clones derived from single cells growing in BUdR as well as in mass populations. These clones appear capable of indefinite growth in vitro in BUdR with altered morphology. The suppression of cytodifferentiation in these melanoma cells and in embryonic cells, coupled with the modification of malignancy, leads to the hypothesis that both differentiation and malignancy are regulated by similar cellular mechanisms. These effects of BUdR offer promise of a powerful tool to probe these regulatory mechanisms.