Acceleration of Growth of Sarcoma 180 with Pyridoxamine and Retardation with Penicillamine.

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Abstract
Summary Pyridoxamine dihydrochloride accelerated the growth of ascitic Sarcoma 180 in CF1 mice and shortened the life span of these tumor bearing animals. It also accelerated the growth of the solid form of the tumor, indicating the strong B6-avidity of this tumor system. Pyridoxine dietary deficiency-alone retarded the growth of the solid form of the tumor, while pyridoxamine nullified this effect. A relatively nontoxic B6 antagonist, L-penicillamine (β-mercaptovaline), used clinically as a chelating agent, was found to retard the growth of solid form S-180 in mice when they were maintained on a complete diet, and especially so on pyridoxine deficient diet. The L-, D- and DL-forms of penicillamine were all active as sarcoma retarding agents, the L-form being the most active. Growth retardation of solid form S-180 was produced by L-penicillamine whether therapy was started 24 hours after tumor implantation or was delayed for 96 hours. L-penicillamine was equally as active as 5-fluoro-uracil in retarding the growth of solid form S-180 in mice maintained on pyridoxine deficient diet and was less toxic. The tumor retarding effect of L-penicillamine was partly-nullified by pyridoxamine, the two compounds acting in vivo as a vitamin and antivitamin pair. Pyridoxamine reversed the life prolonging action of 5-fluorouracil on ascitic S-180-bearing mice and reversed 5-fluorouracil induced weight loss in normal mice. Therapy of a B6-responsive transplantable tumor in mice such as Sarcoma 180, with the use of pyridoxine deficient diet plus administration of L-penicillamine was successful in significantly retarding the in vivo development of the tumor.