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Biosynthesis of a Novel Form of Vitamin B-6 by Tumor Cells^{1, 2,}

Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV 26506

Studies on the time-course utilization of radiolabeled pyridoxine in hepatoma-bearing rats led to the discovery of a novel vitamin B-6 product. It is present in a spectrum of tumor lines, but it is absent or occurs minimally in normal tissues. Hepatomas incorporate up to 20–30% of labeled pyridoxine into the novel species. Its structure was tentatively identified as adenosine-N⁶-methyl, propylthioether-N-pyridoximine-5'-phosphate. In the present study, 3B3 mouse-human hybridoma cells were incubated with radiolabeled precursor molecules, perchloric acid cell extracts were analyzed by high performance liquid chromatography (HPLC), and radioactivity in effluent fractions was measured. The results show that [G-³H]pyridoxine, [2,8-³H]adenosine, L-[³⁵S]cysteine and L-[U-¹⁴C]serine are incorporated into the novel tumor product. These findings are interpreted to indicate that the correct structure of the novel product is adenosine-N⁶-diethylthioether-N'-pyridoximine-5'-phosphate. Further, these data demonstrate that tumor cells have evolved novel enzymatic steps for metabolism of vitamin B-6. The potential use of the novel metabolite as a marker for tumor genesis and establishment is especially significant, as the compound is peculiar to the neoplastic state.

KEY WORDS: • vitamin B-6 • novel tumor product • biosynthesis

¹ Supported by a grant from the Mary Babb Randolph Cancer Center, an award from the Graduate School, and in part by CA 28140 from the National Cancer Institute.

² Presented in part at the First International Symposium on Nutrition, Growth, and Cancer, Athens, Greece, April 26–30, 1987 [J. Nutr. Growth Cancer 4: 70 (abs.)]. This report is a part of the Ph.D. dissertation of R. E. Bishop submitted to the Graduate School of West Virginia University.

³ To whom reprint requests should be addressed.

Manuscript received 29 April 1988. Revision accepted 24 October 1988.