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Vitamin B₆ and Cancer: Synthesis and Occurrence of Adenosine-N⁶-diethylthioether-N-pyridoximine-5'-phosphate, a Circulating Human Tumor Marker¹

Department of Biochemistry [G. P. T., R. E. B., P. K. S.] and Medicine [J. G. A.] and School of Pharmacy [P. M. G., J. R. A.], Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 26506

In the course of studies aimed at deciphering the metabolic transformations of [3,4-¹⁴C] and [³H]C6-pyridoxine hydrochloride by tumor-bearing rats and tumor cells in culture, biosynthesis of a novel labeled product was observed. Its production began with the onset of tumor growth and increased as cell proliferation increased. Chemical, enzymatic, precursor labeling, and analytical tests on the isolated product indicated this product as adenosine-N⁶-diethylthioether-N-pyridoximine-5'-phosphate (compound 1). In confirmation, the chemical synthesis and characterization of compound 1 are presented in this study. In addition, blood samples from 28 normal subjects, 28 cancer patients with different malignancies, and 39 patients with a variety of other than cancer ailments were screened for compound 1 on a blind basis using reverse phase ion-paired high-performance liquid chromatography. The results show that the level of the vitamin B₆ conjugate in the circulation of control subjects, cancer patients in remission, and patients with other diseases was only minimal. Cancer patients with active disease had 3–4-fold higher levels (P < 0.00001). Our results also confirm previous findings regarding the structure of compound 1 and show its potential value as a circulating human tumor marker that could be successfully used for cancer detection.

¹ This work was supported by Grant CA 28140 from the National Cancer Institute, Grant R15 GM 46067 from the NIH, and Grants R-91018 and R-92013 from the West Virginia University Senate Research Committee.

² To whom requests for reprints should be addressed, at Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, P. O. Box 9142, Morgantown, WV 26506-9142. Phone: (304) 293-7754; Fax: (304) 293-6846.

³ Present address: Microbiological Associates, Inc., Life Sciences Center, 9900 Blackwell Road, Rockville, MD 20850-3349.

⁴ Present address: 60 J. Nehru Road, Tagore Town, Allahabad, U.P. 211002, India.

Received 1/22/96. Accepted 6/18/96.