Relationship of antigenicity of melanoma cells grown in 5-bromodeoxyuridine to reduced tumorigenicity.

B16 mouse melanoma cells (clone BS59) grown in 1 to 3 ¿ig of 5-bromodeoxyuridine (BUdR) per ml form few or no tumors in C57BL/6J adult mice when injected subcutaneously in doses at which untreated cells always form tumors. Injections of BUdR-grown cells protect adult mice against melanoma. Melanoma cells grown in 1/ig of BUdR per ml for almost 1 year (clone C3471) retain a plating efficiency similar to that of untreated cells. When C3471 cells are injected into C57BL/6J mice treated with antithymocyte serum or into neonates, tumors grow and kill all the mice. Melanoma cells grown in 3 Mgof BUdR per ml for 14 days form no tumors in normal adult mice, but form tumors and kill 72% of antithymocyte serum-treated adults and 21% of neonates inoculated with IO6 cells. Although their plating efficiency is reduced from control levels, the ability of BUdR-treated melanoma cells to grow in vivo is proved by tumor formation in immunologically compromised mice. Growth in both concentrations of BUdR greatly increases production of a C-type virus. C3471 cells express Gross cell surface antigen, undetectable in control cells, and increase their expression of H-2b antigen. The ability of BUdR-grown cells to protect against melanoma and to form tumors in neonates and antithymocyte serum-treated adults, in contrast to normal adults, and their increased production of virus and of cell surface antigens, all make it likely that one component of the loss of tumorigenicity is a change in antigenicity of these cells.