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

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.