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Basic Sciences

Enzymes of Uracil Catabolism in Normal and Neoplastic Human Tissues

Fardos N. M. Naguib, Mahmoud H. el Kouni and Sungman Cha
Fardos N. M. Naguib
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Mahmoud H. el Kouni
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Sungman Cha
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DOI:  Published November 1985
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Abstract

Enzymes of the pyrimidine base catabolism, dihydrouracil dehydrogenase (EC 1.3.1.2), dihydropyrimidinase (EC 3.5.2.2), and β-ureidopropionase (EC 3.5.1.6) were compared in the cytosolic extract of several normal and neoplastic human tissues. The activity was measured by following the catabolism of [6-14C]-uracil to dihydrouracil, carbamyl-β-alanine, and β-alanine. Substrate inhibition, hysteresis, allosterism, and the lack of dihydropyrimidinase are pointed out as special problems in assaying enzymes of pyrimidine degradation. The activity of dihydrouracil dehydrogenase has been demonstrated in several human extrahepatic tissues and tumors. The enzyme is rate limiting in extrahepatic solid tumors but not in their normal counterparts. Some of these solid tumors contain greater amounts of activity than do their normal equivalents, which encourages the use of inhibitors of this enzyme in conjunction with treatment of these tumors by 5-fluorouracil. Because of the lack of a pattern in dihydrouracil dehydrogenase activity between tumors and normal tissues, the enzyme is not a good marker for tumorigenicity. Dihydropyrimidinase, on the other hand, is highly active in all solid tumors studied but not in their normal counterparts; therefore, we suggest that dihydropyrimidinase can serve as a good marker of tumorigenicity as well as a target for cancer chemotherapy of human solid tumors.

Footnotes

  • ↵1 Supported by Grants CA-31706 and CA-13943 awarded by the National Cancer Institute, Department of Health and Human Services, and Grant CH-136 from the American Cancer Society.

  • ↵2 To whom requests for reprints should be addressed.

  • Received March 18, 1985.
  • Revision received June 9, 1985.
  • Accepted July 22, 1985.
  • ©1985 American Association for Cancer Research.
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November 1985
Volume 45, Issue 11 Part 1
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Enzymes of Uracil Catabolism in Normal and Neoplastic Human Tissues
Fardos N. M. Naguib, Mahmoud H. el Kouni and Sungman Cha
Cancer Res November 1 1985 (45) (11 Part 1) 5405-5412;

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Enzymes of Uracil Catabolism in Normal and Neoplastic Human Tissues
Fardos N. M. Naguib, Mahmoud H. el Kouni and Sungman Cha
Cancer Res November 1 1985 (45) (11 Part 1) 5405-5412;
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