Purine Enzymology of Human Colon Carcinomas

Yutaka Natsumeda, May S. Lui, Jahangir Emrani, Mary A. Faderan, Melissa A. Reardon, John N. Eble, John L. Glover, George Weber

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The purpose of this study was to elucidate the purine enzymic programs of human primary colorectal carcinomas. Marked alteration in the enzymology of the human colon neoplasm clearly distinguished it from that of the normal colon mucosa. In the human colon mucosa, the activities of ribonucleotide reductase, inosine phosphate dehydrogenase, formylglycinamidine ribonucleotide synthetase, guanosine phosphate synthetase, and ami-dophosphoribosyttransferase were 0.042, 5.2,5.6, 8.2 and 36.0 nmol/h/mg protein, respectively, and in the colon carcinomas the activities increased to 755, 575, 295, 280, and 294% of the normal values. The activities of the salvage enzymes, adenine and hypoxanthine-guanine phosphoribosyltransferases, were 310, 249, and 602 nmol/h/mg protein, respectively, whereas in the tumors, only the activity of adenine phosphoribosyltransferase was increased (2-fokj). The markedly higher absolute enzymic capacity for salvage in the tumors accounts, in part at least, for the lack of chemotherapeutic success of inhibitors of enzymes of de novo synthesis that have been used in the clinical treatment of colorectal carcinomas. Combinations of inhibitors of de novo biosynthesis and blockers of the salvage enzymes or of salvage transport (e.g., dipyridamole) should improve the chemotherapy of colon neoplasms. Since in the colon carcinoma the activities of glutamine-utilizing enzymes (guanosine phosphate and formylglycinamidine ribonucleotide synthetase and amidophosphoribosyttransferase) were markedly increased, and the glutamine concentration was decreased (50%), treatment with an antiglutamine agent (e.g., acivicin) should be of relevance. Since the activity of ribonucleotide reductase, the rate-limiting enzyme of nucleic acid biosynthesis, was markedly increased in the colon neoplasms, combination chemotherapy might include drugs against this enzyme.

Original languageEnglish (US)
Pages (from-to)2556-2559
Number of pages4
JournalCancer Research
Volume45
Issue number6
StatePublished - Jun 1 1985

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Natsumeda, Y., Lui, M. S., Emrani, J., Faderan, M. A., Reardon, M. A., Eble, J. N., Glover, J. L., & Weber, G. (1985). Purine Enzymology of Human Colon Carcinomas. Cancer Research, 45(6), 2556-2559.