Pharmacological perturbation of murine melanoma growth by copper chelates

Groups of BDF1 and DBA mice were treated with either the cupric chelate of nitrilotriacetic acid (NTA-Cu+2) or the cuprous chelate of neocuproine (NC-Cu+1) every other day for 7 days prior to either i.p. or s.c. inoculation with 10(6) viable B16 melanoma cells, and then every other day for 15 days post-tumor inoculation. This treatment schedule was non-toxic to host mice. NC-Cu+1 acted as a tumor growth promoting factor in mice by enhancing tumorigenicity, stimulating body weight gain, inhibiting encapsulation of i.p. tumors that permitted growth as unrestrained ascites, and increasing final tumor weight over a shortened host survival period regardless of the site of tumor inoculation. Treatment with NTA-Cu+2 inhibited pigmentation in DBA mice bearing s.c. tumors, while treatment with NC-Cu+1 enhanced tumor pigmentation regardless of the site of tumor inoculation and murine strain. These results suggest that exogenous copper in the form of chelates alters the growth characteristics of a copper-requiring tumor system in both a copper-chelate- and murine-specific manner, and further suggests that the growth promoting activity of exogenous copper in the B16 melanoma system involves both enhanced copper nutrition and concomitant alteration of host reactions to tumors.