Induction of transplantable melanoma by treatment with N-methyl-N'-nitro-N-nitrosoguanidine in an inbred strain of the teleost Oryzias latipes

Abstract

Adult fish of two different inbred strains (HO4C and HB32C) of Oryzias latipes that were established in this laboratory were exposed for 2 hours to an aqueous solution of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] at concentrations from 20 to 100 ppm. The acute toxicity and carcinogenicity of MNNG differed between two inbred strains. Almost no tumors were observed in strain HO4C fish, although these fish were sensitive to the acute toxicity of MNNG, with the median lethal dose being 28 ppm at 48 hours after the treatment. In contrast, in the HB32C strain, a dose-related tumorigenic response was observed, with the median lethal dose being 38 ppm at 48 hours after treatment. Most MNNG-induced tumors were considered amelanotic melanomas on the basis of histologic findings and a positive dopa reaction in selected samples. By the technique of transplantation of tumor tissue into the eye chamber and intraperitoneal cavity of fish of the syngeneic strain, serial transplantation of the tumor was successful. Tumor transplantation into one of the allogeneic strains (HO5) was also successful. The tumors have now been serially grown in the eye chambers in syngeneic fish for more than 14 generations.