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Effect of Phorbol Ester Tumor Promoters on the Expression of Melanogenesis in B-16 Melanoma Cells¹

Division of Environmental Sciences [I. B. W.] and Institute of Cancer Research [I. B. W., R. A. M., P. B. F.], Columbia University College of Physicians and Surgeons, New York, New York 10032

Cells of the C₃ clone of B-16 melanoma synthesize melanin only at confluence after which they senesce and can no longer be passaged. Addition to the cultures of 10^–8–10^–7 M 12-O-tetradecanoylphorbol-13-acetate (TPA) shortly after plating delayed by about 2 days the onset of melanogenesis. TPA did not, however, affect the growth of the cells or the time at which they reached confluence. The ability of a series of phorbol esters to delay melanogenesis correlated with their tumor-promoting activity on mouse skin. The optimum time for addition of TPA was within the first 24 hr after plating; the inhibitory effect decreased when TPA was added at later points. -melanocyte-stimulating hormone (5 x 10^–7 M) added to B-16 cultures 24 hr after plating slowed the growth of the cells and caused them to differentiate when still subconfluent. TPA also inhibited this -melanocyte-stimulating hormone-induced melanogenesis.

These results suggest that TPA inhibits a very early stage in a stepwise process that leads to the differentiation of these cultures. For reasons that are not apparent, the cells eventually escape from this inhibition. The B-16 melanoma cell culture system may be useful for studying the mechanism by which TPA and related tumor promoters affect cellular differentiation.

¹ This work was supported by National Cancer Institute Contract 1-CP-2-3234 and American Cancer Society Grant RD-50.

² To whom requests for reprints should be addressed.

Received 1/ 2/79. Accepted 6/27/79.

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