Comparison of Urinary Modified Nucleosides and Bases in Rats with Hepatomas and Nephroblastomas

  • I. Clark
  • J. W. MacKenzie
  • J. R. McCoy
  • W. Lin
Part of the Recent Results in Cancer Research/Fortschritte der Krebsforschung/Progrès dans les recherches sur Ie cancer book series (RECENTCANCER, volume 84)


It has been known for more than 20 years that patients with cancer excrete greater than normal amounts of purine and pyrimidine derivatives in their urines (Adams et al. 1960; Park et al. 1962). The unmodified purine derivatives, adenine and guanine, are normally metabolized to uric acid, but in some instances they are not metabolized further and may be excreted or recycled into nucleic acids. The unmodified pyrimidine derivatives, cytosine and uracil, are usually degraded and excreted as ammonia and urea, but recycling and excretion may occur. It was not until the pioneering studies by Borek and his students on tRNA methyltransferases (Fleissner and Borek 1963) that the methylated nucleosides in the urine were shown to be derived from tRNA (Mandel et al. 1966). More recently, using more sensitive techniques, several groups of investigators have reported increased levels of modified nucleosides in urines from patients with cancer (Hogan et al. 1970; Waalkes et al. 1973; Mrochek et al. 1974; Senftleber et al. 1976; Davis et al. 1977; Gehrke et al. 1978; Speer et al. 1979; Hartwick et al. 1980). The increased levels of most modified nucleosides and bases in urine of hosts with neoplasms have been attributed to an increased rate of turnover of tRNA in cancer tissue (Borek et al. 1977). The evidence to date suggests that modified nucleosides or bases are not metabolized further and are quantitatively excreted into the urine (Weissman et al. 1962; Dlugajczyk and Eiler 1966). More than 20 modified nucleosides have been isolated from human urine (Chedda 1975).


Posterior Silk Gland Modify Nucleoside Methylase Activity Urinary Pattern Urinary Nucleoside 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.









N 2 2 dimethylgua-nosine
























ultraviolet light




high-pressure liquid chromatography


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams WS, Davis F, Nakatani M (1960) Purine and pyrimidine excretion in normal and leukemic subjects. Am J Med 28: 726–734PubMedCrossRefGoogle Scholar
  2. Borek E, Baliga BS, Gehrke CW et al. (1977) High turnover rate of transfer RNA in tumor tissue. Cancer Res 37:3362–3366PubMedGoogle Scholar
  3. Bradford DS, Hacker B, Clark I (1972) Transfer ribonucleic acid methylases of bone: Studies on vitamin A and D deficiency. Biochem J 126: 1057–1066PubMedGoogle Scholar
  4. Chedda CB (1975) In: Fasman G (ed) The handbook of biochemistry and molecular biology, vol I. Chemical Rubber Co., Cleveland Ohio, p251Google Scholar
  5. Clark I, Trebilcock-Guzman M (1979) Improved separation of modified nucleosides from tRNA hydrolysate: The patterns of tRNA methylation in rat tissue. J Biochem and Biophys Methods 1:287–298CrossRefGoogle Scholar
  6. Datta RK, Datta B (1969) Role of methylated nucleic acids in carcinogenesis. Exp Mol Pathol 10:129–140PubMedCrossRefGoogle Scholar
  7. Davis GE, Suits RD, Kuo KC, Gehrke CW, Waalkes TP, Borek E (1977) High-performance liquid chromatographic separation and quantification of nucleosides in urine and some other biological fluids. CUn Chem 23: 1427–1435Google Scholar
  8. Desrosiers R, Frederici K, Rottman F (1974) Identification of methylated nucleosides in messenger RNA from Novikoff Hepatoma cells. Proc Natl Acad Sci USA 71: 3971–3975PubMedCrossRefGoogle Scholar
  9. Dlugajczyk A, Eiler JJ (1966) Lack of catabolism of 5-ribosyluracil in man. Nature 212:611–612PubMedCrossRefGoogle Scholar
  10. Dunn DB, Hall RH (1975) In: Fasman G (ed) The handbook of biochemistry and molecular biology, vol I. Chemical Rubber Co, Cleveland OhioGoogle Scholar
  11. Fleissner E, Borek E (1963) Studies on the enzymatic methylation of soluble RNA. Biochemistry 2: 1093–1100PubMedCrossRefGoogle Scholar
  12. Garel JP, et al. (1976) Structural studies on RNA from Bombyx mori L. I. Nucleoside composition of enriched tRNA species from posterior silk gland purified by counter current distribution. Biochimie 58: 1089–1100PubMedCrossRefGoogle Scholar
  13. Gehrke CW, Kuo KC, Davis GE, Suits RD, Waalkes TP, Borek E (1978) Quantitative high-performance liquid chromatography of nucleosides in biological material. J Chromatogr 150: 455–476PubMedCrossRefGoogle Scholar
  14. Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) Patterns of urinary excretion of modified nucleosides. Cancer Res 39: 1150–1153PubMedGoogle Scholar
  15. Hancock RL, Forrester PI (1973) Increase of soluble RNA methylase activities by chemical carcinogens. Cancer Res 33: 1747–1753PubMedGoogle Scholar
  16. Hancock RL, McFarland P, Fox RR (1967) sRNA methylase activity of embryonic liver. Experientia 23: 806–807PubMedCrossRefGoogle Scholar
  17. Hartwick RA, Krstulovic AM, Brown PR (1979) Identification and quantitation of nucleosides, bases and other UV absorbing compounds in serum, using reversed phase high performance liquid chromatography. II. Evaluation of human sera. J Chromatogr 186: 659–676PubMedCrossRefGoogle Scholar
  18. Hogan A, Creuss-Callaghan MB, Fenelly JJ (1970) Studies of pseudouridine changes in chronic lymphatic leukemia during therapy. Irish J Med Sci 3: 505–511CrossRefGoogle Scholar
  19. Mandel LR, Srinivasan PR, Borek E (1966) Origins of urinary methylated purines. Nature 209:586–588PubMedCrossRefGoogle Scholar
  20. McFarlane ES, Shaw GJ (1968) Observed increase in methylated purines excreted by hamsters bearing adenovirus-12 induced tumors. Can J Microbiol 14: 135–187Google Scholar
  21. Mrochek JE, Dinsmore SR, Waalkes TP (1974) Analytic techniques in the separation and identification of specific purine and pyrimidine.degradation products of tRNA: application to urine samples from cancer patients. J Natl Cancer Inst 53: 1553–1563PubMedGoogle Scholar
  22. Park RW, Holland JF, Jenkins A (1962) Urinary purines in leukemia. Cancer Res 22:469–477PubMedGoogle Scholar
  23. Randerath E, Chia LL, Morris HP, Randerath K (1974) Transfer RNA base composition studies in Morris hepatomas and rat liver. Cancer Res 34:643–653PubMedGoogle Scholar
  24. Roe BA, Stankiewicz AF, Rizi HL, Weisz C, DiLauro MN, Pike D, Chen C, Chen E (1979) Comparison of rat liver and Walker 256 carcinosarcoma tRNAs. Nucleic Acids Res 8:673–688CrossRefGoogle Scholar
  25. Rottman FM (1978) In: Clark BFC (ed) International review of biochemistry, biochemistry of nucleic Acids II, Vol 17. Methylation and polyadenylation of heterogeneous nuclear and messenger RNA, pp 45–73Google Scholar
  26. Senftleber FC, Halline AG, Veening H, et al. (1976) Reversed phase liquid chromatographic analysis of hemodialysate from uremic patients. Clin Chem 22: 1522–1527PubMedGoogle Scholar
  27. Shatkin AJ (1976) Capping of eucaryotic mRNAs. Cell 9:645–653PubMedCrossRefGoogle Scholar
  28. Speer J, Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) tRNA breakdown products as markers for cancer. Cancer 44: 2120–2123PubMedCrossRefGoogle Scholar
  29. Stewart BW, Pegg AE (1972) Changes in tRNA methylase activity of rat kidney following administration of the carcinogen dimethylnitrosamine. Biochim Biophys Acta 281:416–424PubMedGoogle Scholar
  30. Tsutsui E, Srinivasan PR, Borek E (1966) tRNA methylases in tumors of animal and human origin. Proc Natl Acad Sci USA 56: 1003–1009PubMedCrossRefGoogle Scholar
  31. Waalkes TP, Dinsmore SR, Mrochek JE (1973) Urinary excretion by cancer patients of the nucleosides N-dimethylguanosine, 1-methylinosine and pseudouridine. J Natl Cancer Inst 51: 271–274PubMedGoogle Scholar
  32. Weissman S, Eisen AZ, Lewis M, Karon M (1962) Pseudouridine metabolism. III. Studies with isotopically labeled pseudouridine. J Lab Clin Med 60:40–47PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin • Heidelberg 1983

Authors and Affiliations

  • I. Clark
    • 1
  • J. W. MacKenzie
    • 1
  • J. R. McCoy
    • 1
  • W. Lin
    • 1
  1. 1.Departments of Surgery, Biochemistry, and PathologyCMDNJ-Rutgers Medical SchoolPiscatawayUSA

Personalised recommendations