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An Amelanotic Variant of B16 Malignant Melanoma¹

Department of Cutaneous Biology, Oregon Regional Primate Research Center, Beaverton, Oregon 97005

Murine malignant melanoma (B16) cells tolerant to 10 and 30 µg of BrdU pcr ml were maintained for more than one year in culture medium lacking the analog. The analog-containing environment was also eliminated by the injection of cells at several subcultures into host animals. Cells withdrawn from BrdU retained the enlarged, flattened, nonpigmented morphology that is characteristic of analog-treated cells. In 465 tumors, only 10 possessed pigmented nodules; all 10 originated from one culture that may have been contaminated with pigmented cells from control cultures. Although possible, it is not likely that the pigmented cells represented revertants, because they have never been noted since February 1971.

Possible mechanisms that explain our observations include (a) the interference by BrdU at high concentrations with the synthesis of transcriptional or translational molecules which, once depleted, are not renewed; (b) the selection of a rare amelanotic variant initially present in the culture; and (c) the induction of mutation(s) by BrdU that result in amelanotic cells.

¹ Publication No. 579 from the Oregon Regional Primate Research Center, supported in part by Grants RR-05694 and FR-00163 from the NIH, Grant CA 08499 from the National Cancer Institute, and by funds from Cammack Trust, Portland, Ore.

Received 3/20/72. Accepted 5/ 4/72.