Isolation and characterization of Lymphomycin

A new antitumor antibiotic is produced in fermentation broths by Streptomyces sp. S-66. This material, named lymphomycin, was isolated on the basis of inhibition of mouse leukemia SN-36 in mice, and toxicity to BURKITT lymphoma cells in tissue culture. It was precipitated from filtered broth with ammonium sulfate and purified by chromatography on columns of Sephadex and carboxymethyl cellulose. Lymphomycin is a black-colored, acidic protein with a molecular weight of about 11, 000 and valine as an N-terminal amino-acid. It contains no carbohydrates or nucleic acids. It is soluble in water, insoluble in most organic solvents, and is relatively stable in water over the pH range, 5 to 7. It has no distinct absorption maximum in its spectrum. Lymphomycin has no inhibitory activity against bacteria, yeast, fungi and mycoplasmas tested so far. It is cytotoxic to Burkitt lymphoma and human lymphoblastoid cells and peritoneal macrophages, but not inhibitory to human epidermoid carcinoma HeLa, mouse fibroblast L, chick embryo, calf kidney and mouse adenocarcinoma FM3A cells in tissue culture. Lymphomycin is lethal to tumor-bearing mice at 80 mg/kg of body weight per day when given intraperitoneally once daily for 6 days, but not toxic at 40 mg/kg/day. Tests with transplanted rodent tumors indicate that the antibiotic is inhibitory to the growth of both solid and ascitic forms of Sarcoma 180 and lymphatic leukemia SN-36 in mice. The growth of solid tumor of a fibrosarcoma in hamsters was also inhibited at optimal daily doses of 0.8 and 2 mg/kg. Lymphomycin has no effect on the growth of the solid forms of Ehrlich and Bashford carcinoma in mice.