Vitamin B6 and cancer: synthesis and occurrence of adenosine-N6-diethylthioether-N-pyridoximine-5'-phosphate, a circulating human tumor marker.
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.
Tryfiates
G P
GP
Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506, USA.
Gannett
P M
PM
Bishop
R E
RE
Shastri
P K
PK
Ammons
J R
JR
Arbogast
J G
JG
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051381:Rats
D014408:Biomarkers, Tumor; C058697:adenosine-N(6)-diethylthioether-N'-pyridoximine 5'-phosphate; D000241:Adenosine; D011736:Pyridoxine