Characterisation of human malignant melanoma cell lines. VI. Inhibition of 3H-thymidine uptake by normal stimulated lymphocytes.

Cultured human malignant melanoma cells, when added to normal human lymphocytes stimulated to proliferate by mitogen or antigen, were found to inhibit the uptake of 3H-thymidine (3H-T) by the lymphocytes. A heat-labile factor present in the supernatants of the melanoma cultures is responsible for inhibition. Cell viability and blastogenesis are unimpaired in the lymphocyte cultures containing the inhibitor. Inhibition of 3H-deoxyuridine uptake was also noted indicating that both salvage and de novo pathways of DNA synthesis are involved. Lymphocytes appear to be preferentially affected as cultured colon cancer cells take up 3H-T normally in the presence of the inhibitor. Normal mitotic indices and biochemical estimation of DNA content in lymphocyte cultures containing the inhibitory factor indicate that DNA synthesis does proceed normally. The mechanisms of action of the inhibitor would appear to involve alteration of exogenous nucleoside rather than a metabolic inhibition of intracellular nucleic acid synthesis.