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Elevated urinary levels of 6‐hydroxymethylpterin during malignancy and liver regeneration: A simple, noninvasive test for cancer detection

A simple and rapid method for determining urinary 6‐hydroxymethylpterin levels is described. It involves adsorption of the pterin compound from deproteinized urine samples on activated charcoal under acidic conditions and its subsequent elution under alkaline conditions in a concentration suitable for its spectrophotofluorometric quantitation. The major blue fluorescent compound being measured was identified as 6‐hydroxymethylpterin by thin layer chromatography on combined Silica gel‐G and cellulose. While 30 healthy human subjects excreted 6‐hydroxymethylpterin at a mean level of 0.121 μg/ml of urine, 120 patients with various types of cancer excreted very significantly higher levels ranging from 0.3 to 2.0 μg/ml. The mean excretion level for 19 patients with various nonmalignant diseases was 0.134 μG/ml which was not significantly different from that for the healthy control subjects. In two experimental model systems described, following partial hepatectomy and the induction of Yoshida ascites tumors in rats, the peak periods of liver regeneration and maximal tumor growth were accompanied, respectively, by four and 40‐fold increases in urinary 6‐hydroxymethylpterin excretion. Ingestion of multivitamin tablets containing 5 mg of folic acid (but not rich dietary sources of folates) resulted in temporary elevation of urinary 6‐hydroxymethylpterin levels. The method described for determining urinary 6‐hydroxymethylpterin provides a simple, noninvasive means of detecting prevailing malignancies.