Pterin-6-aldehyde, a cancer cell catabolite: identification and application in diagnosis and treatment of human cancer.

Halpern R; Halpern BC; Stea B; Dunlap A; Conklin K; Clark B; Ashe H; Sperling L; Halpern JA; Hardy D; Smith RA

doi:10.1073/pnas.74.2.587

Pterin-6-aldehyde, a cancer cell catabolite: identification and application in diagnosis and treatment of human cancer.

Halpern R, Halpern BC, Stea B, Dunlap A, Conklin K, Clark B, Ashe H, Sperling L, Halpern JA, Hardy D, Smith RA

Proceedings of the National Academy of Sciences of the United States of America · 1977 · doi:10.1073/pnas.74.2.587 · PMID:265525 · PMC392336

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Cancer cells uniquely degrade folic acid into pterin-6-aldehyde, which is detectable in the urine of patients with active tumors but absent after complete tumor resection.

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The study identifies pterin-6-aldehyde as a unique catabolite produced by the active degradation of folic acid, a metabolic process observed exclusively in cancer cells in tissue culture and not in normal adult epithelial or fibroblastic cells. Analysis of first-morning urine samples from twenty-nine patients revealed that levels of this compound at approximately 300 nmol/ml or greater were present only in those with a confirmed tissue diagnosis of cancer, whereas healthy individuals did not exhibit these levels unless their diets were supplemented with folic acid. The researchers further noted that following the total resection of cancerous tissue, pterin-6-aldehyde was no longer detectable in the patients' urine postoperatively, indicating its potential utility as a diagnostic marker for malignancy. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Active folic acid degradation with the formation pterin-6-aldehyde is a previously undescribed characteristic of cancer cells in tissue culture. Neither normal adult epithelial and fibroblastic cells nor human amniotic cells nor mouse embryonic fibroblasts degrade folic acid to a measurable degree. Twenty-nine patients whose diagnoses were not revealed until after the test of their first morning urine for pterin-6-aldehyde was completed were studied for the presence or absence of pterin-6-aldehyde by thin-layer chromatography. Pterin-6-aldehyde was found in the urine at about 300 nmol/ml or greater only in those 13 patients with a tissue diagnosis of cancer. When the cancer was totally resected, the pterin-6-aldehyde was no longer found in the urine postoperatively. Pterin-6-aldehyde is not found in the urine of healthy patients at this level of detection unless their diets are supplemented with folic acid.

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Abstract Active folic acid degradation with the formation pterin-6-aldehyde is a previously undescribed characteristic of cancer cells in tissue culture. Neither normal adult epithelial and fibroblastic cells nor human amniotic cells nor mouse embryonic fibroblasts degrade folic acid to a measurable degree. Twenty-nine patients whose diagnoses were not revealed until after the test of their first morning urine for pterin-6-aldehyde was completed were studied for the presence or absence of pterin-6-aldehyde by thin-layer chromatography. Pterin-6-aldehyde was found in the urine at about 300 nmol/ml or greater only in those 13 patients with a tissue diagnosis of cancer. When the cancer was totally resected, the pterin-6-aldehyde was no longer found in the urine postoperatively. Pterin-6-aldehyde is not found in the urine of healthy patients at this level of detection unless their diets are supplemented with folic acid. Full text PDFSelected References These references are in PubMed. This may not be the complete list of references from this article. - ALLEN B., DAY P. L., DINNING J. S., SIME J. T., WORK P. S. The metabolic conversion of folic acid and citrovorum factor to a diazotizable amine. Arch Biochem Biophys. 1957 Jan;66(1):114–119. doi: 10.1016/0003-9861(57)90540-4. [DOI] [PubMed] [Google Scholar] - BLAIR J. A. Isolation of isoxanthopterin from human urine. Biochem J. 1958 Mar;68(3):385–387. doi: 10.1042/bj0680385a. [DOI] [PMC free article] [PubMed] [Google Scholar] - BLAIR J. A. Some observations on the oxidative degradation of pteroyl-L-glutamic acid. Biochem J. 1957 Feb;65(2):209–211. doi: 10.1042/bj0650209a. [DOI] [PMC free article] [PubMed] [Google Scholar] - BRAGANCA B. M., ARAVINDAKSHAN I., GHANEKAR D. S. Enzymic cleavage of folic acid by extracts from human blood cells. I. Preparation and co-factor requirements of the enzyme system. Biochim Biophys Acta. 1957 Sep;25(3):623–634. doi: 10.1016/0006-3002(57)90536-x. [DOI] [PubMed] [Google Scholar] - FUTTERMAN S., SILVERMAN M. The inactivation of folic acid by liver. J Biol Chem. 1957 Jan;224(1):31–40. [PubMed] [Google Scholar] - Fukushima T. Biosynthesis of pteridines in the tadpole of the bullfrog, Rana catesbeiana. Arch Biochem Biophys. 1970 Aug;139(2):361–369. doi: 10.1016/0003-9861(70)90488-1. [DOI] [PubMed] [Google Scholar] - Fukushima T., Shiota T. Pterins in human urine. J Biol Chem. 1972 Jul 25;247(14):4549–4556. [PubMed] [Google Scholar] - JOHNS D. G., SPERTI S., BURGEN A. S. The metabolism of tritiated folic acid in man. J Clin Invest. 1961 Sep;40:1684–1695. doi: 10.1172/JCI104391. [DOI] [PMC free article] [PubMed] [Google Scholar] - Wright L. D., Welch A. D. THE PRODUCTION OF FOLIC ACID BY RAT LIVER IN VITRO. Science. 1943 Aug 20;98(2538):179–182. doi: 10.1126/science.98.2538.179. [DOI] [PubMed] [Google Scholar]

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