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The Inhibition of Growth of Sarcoma 180 by Combinations of B₆-Antagonists and Acid Hydrazides^*

( Kettering-Meyer Laboratory [Affiliated with Sloan-Kettering Institute], Southern Research Institute, Birmingham, Alabama)

1. Deoxypyridoxine hydrochloride and deoxypyridoxine phosphate are without effect on Sarcoma 180 growth in mice on a complete diet.

2. Deoxypyridoxine hydrochloride and deoxypyridoxine phosphate significantly restrict Sarcoma 180 growth in mice maintained on a B₆-deficient diet.

3. With the exception of 1,5-diaminobiuret administered at high dosage levels, acid hydrazides are without effect on Sarcoma 180 growth in mice on a complete diet. Many compounds of this type exhibit a significant restricting effect on Sarcoma 180 growth in mice on a B₆-deficient diet.

4. Combinations of deoxypyridoxine phosphate with acid hydrazides appear to be more inhibitory to Sarcoma 180 growth in mice on a complete diet than are combinations of deoxypyridoxine hydrochloride with acid hydrazides.

5. These same combinations administered to mice maintained on a B₆-deficient diet result in severe restriction of Sarcoma 180 growth. At higher drug levels the combinations are toxic; however, low levels of the combinations of drugs are not excessively toxic and are more effective tumor inhibitors than high levels of either drug alone.

6. Vitamins of the B₆ group almost completely prevent the restriction of Sarcoma 180 growth effected by these inhibitory combinations.

7. Spectrophotometric studies demonstrate the ability of representative acid hydrazides to react with pyridoxal phosphate.

8. The observed ability of acid hydrazides to enhance the inhibition of Sarcoma 180 produced by B₆-deficiency and B₆-antagonists can be interpreted by considering that the acid hydrazide forms an inactive conjugate with pyridoxal phosphate, which results in further depletion of vitamin B₆ and marked restriction of tumor growth.

^* The work reported herein was supported by a grant from the American Cancer Society and by a grant (C-2553) from the National Cancer Institute of the National Institutes of Health, Public Health Service.

Received 3/29/56.