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Metabolism of Tetrahydrohomofolate (NSC 89473) in Mice¹

Microbiological Associates, Inc., [L. C. M., A. S. P.], and National Cancer Institute [J. A. R. M.], Bethesda, Maryland 20014

The study has shown that tetrahydrohomofolate (H₄HF)-³H appears to be metabolized in mice. A large amount of the drug-derived radioactivity (60%) could not be accounted for in feces and urine during an 8-day period. This suggested that some of the metabolites and/or decomposition products might have been reutilized and/or retained by the body. A significant amount (24 to 95% of the radioactivity was present as Bratton-Marshall reagent-negative material in all the organs, particularly in the brain and spleen. Since some cofactor forms of H₄HF are negative to bratton-Marshall reagent, the formation of Bratton-Marshall reagent-negative material from H₄HF may be indicative of activation of H₄HF, possibly by the tetrahydrofolate-activating enzymes. Column chromatography of brain and spleen extracts from H₄HF-treated mice has revealed several labeled compounds, none of which was identifiable.

¹ These studies supported in part by Contract N01-CM-33728 with Division of Cancer Treatment, National Cancer Institute, NIH, Department of Health, Education and Welfare, Bethesda, Md. 20014.

² To whom reprint requests should be addressed at Cancer Chemotherapy Department, Microbiological Associates, Inc., 5221 River Road, Bethesda, Md. 20016.

Received 9/13/73. Accepted 1/25/74.