Advertisement

Modified Nucleosides in Body Fluids of Tumor-Bearing Patients

  • F. Salvatore
  • A. Colonna
  • F. Costanzo
  • T. Russo
  • F. Esposito
  • F. Cimino
Part of the Recent Results in Cancer Research/Fortschritte der Krebsforschung/Progrès dans les recherches sur Ie cancer book series (RECENTCANCER, volume 84)

Abstract

The multifunctional cellular role of tRNA is derived from its molecular structure, which is attained through a complex process of biosynthesis, including covalent modifications of many nucleosides (see Salvatore et al. 1982). In fact tRNA is the nucleic acid species which contains the highest and most varied number of modified nucleosides: among the tRNA species analyzed, more than 40 positions along the primary structure have been found occupied by a modified nucleoside (see Agris 1980). About 50 different types of modified nucleosides have been identified, and in a single tRNA species up to 15 of them can be present. In most cases, three or four are ψ residues and between four and ten are methylated nucleosides (see Dirheimer et al. 1979).

Keywords

Chick Embryo Fibroblast Histiocytic Lymphoma tRNA Species Modify Nucleoside Morris Hepatoma 
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.

Abbreviations

ß-AIB

ß-aminoisobutyric acid

ψ

pseudouridine

ψMP

pseudouridine 5′-phosphate

m7I

7-methylinosine

U

uridine

m1A

1-methyladenosine

m7X

7-methylxanthosine

m5C

5-methylcytidine

dU

deoxyuridine

m7G

7-methylguanosine

I

inosine

m5U

5-methyluri-dine

G

guanosine

A

adenosine

C

cytidine

m3U

3-methyluridine

s4U

4-thiouridine

m1I

1-methylinosine

m1G

1-methylguanosine

m2G

N 2-methylguanosine

ac4C

N 4-acetylcytidine

m22G

N 2,N 2-dimethylguanosine

dA

deoxyadenosine

dG

deoxyguanosine

Cm

2′-O-meth-ylcytidine

Gm

2′-O-methylguanosine

dTMP

thymidine 5′-phosphate

Tm

2′-O-methylri-bothymidine

hU

dihydrouridine

t6A

N 6-threonyladenosine

Y

α-(carboxyamino)-4,9-dihy-dro-4,6-dimethyl-9-oxo-lH-imidazol[l,2-α]-purine-7-butyric acid dimethyl ester

Q

7-(4,5-cw-dihydroxy-l-cyclopenten-3-ylaminomethyl)-7-deazaguanosine

m22Gua

N 2,N 2-dimeth-ylguanine

IS

internal standard

AUFS

absorbance units full scale

psi

pounds per square inch

A260 unit

quantity of material contained in 1 ml solution which has an absorbance of 1.0 at 260 nm when measured in 1-cm lightpath cell

GLC

gas-liquid chromatography

RPC

reverse-phase chromatography

HPLC

high-performance liquid chromatography

RIA

radioimmunoassay

SVP

snake venom phosphodiesterase

TCA

trichloracetic acid

EDTA

ethylenediaminetetraacetate

CEF

chick embryo fibroblasts

CEF(RSV)

chick embryo fibroblasts transformed by Rous sarcoma virus

AMY

avian myeloblastosis virus

VERO

cell line derived from African green monkey kidney

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agris PF (1980) The modified nucleosides in tRNA. Liss, New YorkGoogle Scholar
  2. Borek E, Kerr SJ (1972) Atypical transfer RNA’s and their origin in neoplastic cells. Adv Cancer Res 15:163–190PubMedCrossRefGoogle Scholar
  3. Borek E, Baliga BS, Gehrke CW, Kuo KC, Belman S, Troll W, Waalkes TP (1977) High turnover rate of transfer RNA in tumor tissue. Cancer Res 37: 3362–3366PubMedGoogle Scholar
  4. Borek E, Gehrke CW, Waalkes TP (1979) Aberrant methylation of tRNA in tumor tissue. In: Usdin E, Borchardt RT, Creveling CR (eds) Transmethylation. Elsevier North Holland Inc., New York Amsterdam Oxford, pp 457–464Google Scholar
  5. Brunke KJ, Strickler G, Leboy PS (1980) Elevated methylation capacity of selected transfer RNA methyltransferases from 9,10-dimethyl-l,2-benzanthraceneinduced rat mammary tumors. Cancer Res 40:417–423PubMedGoogle Scholar
  6. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31: 1860–1861PubMedGoogle Scholar
  7. Chambers RW (1966) The Chemistry of pseudouridine. Prog Nucleic Acid Res Mol Biol 5:349–398PubMedCrossRefGoogle Scholar
  8. Chheda GB (1970) Purine and pyrimidine derivatives excreted in human urine. In: Sober HA (ed) Handbook of biochemistry, 2nd edn. The Chemical Rubber Co., Cleveland, Ohio, pp G-106-G–113Google Scholar
  9. Cimino F, Costanzo F, Russo T, Colonna A, Esposito F, Salvatore F (1982) Modified nucleosides from transfer ribonucleic acid as tumor markers. In: Usdin E, Borchardt RT, Creveling CR (eds) Biochemistry of S-Adenosyl-methionine and related compounds. MacMillan, London, pp 409–412Google Scholar
  10. Colonna A, Costanzo F, De Caterina M, Salvatore F, Cimino F (1980) High performance liquid chromatography of mpdified nucleosides in the urine of cancer patients, (abstr). Commun 1st Congress of the Italian Society of Clinical Biochemistry, Milan pp 330Google Scholar
  11. Colonna A, Russo T, Cimino F, Salvatore F (1981) Modified nucleosides in biological fluids of cancer patients determined by high performance liquid chromatography. J Clin Chem Clin Biochem 19: 640Google Scholar
  12. Davis GE, Suits RD, Kuo KC, Gehrke CW, Waalkes TP, Borek E (1977) High-performance liquid chromatographic separation and quantitation of nucleosides in urine and some other biological fluids. Clin Chem 23: 1427–1435PubMedGoogle Scholar
  13. Dirheimer G, Keith G, Sibler AP, Martin RP (1979) The primary structure of tRNAs and then-rare nucleosides. In: Schimmel PR, Söll D, Abelson JN (eds) Transfer RNA: Structure, properties and recognition. Cold Spring Harbor Laboratory, pp 19–41Google Scholar
  14. Gehrke CW, Kuo KC, Davis GE, Suits RD, Waalkes TP, Borek E (1978) Quantitative high-performance liquid chromatography of nucleosides in biological materials. J Chro-matogr 150:455–476CrossRefGoogle Scholar
  15. Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) Patterns of urinary excretion of modified nucleosides. Cancer Res 39: 1150–1153PubMedGoogle Scholar
  16. Gionti E, Arcari P, Costanzo P, Salvatore F, Cimino F (1980) Studies on tRNA patterns in normal and Rous Sarcoma virus transformed chick embryo fibroblasts. Embo-FEBS tRNA Workshop, Strasbourg, FranceGoogle Scholar
  17. Grunberger D, Weinstein IB (1975) Deficiency of the Y base in a hepatoma phenylalanine tRNA. Nature 253:66–67PubMedCrossRefGoogle Scholar
  18. Hartwick RA, Krstulovic AM, Brown PR (1979) Identification and quantitation of nucleosides, bases and other UV-absorbing compounds in serum using reverse-phase high-performance liquid chromatography-II. Evaluation of human sera. J Chromatogr 186: 659–676PubMedCrossRefGoogle Scholar
  19. Heinrikson RL, Goldwasser E (1964) Studies on the biosynthesis of 5-ribosyluracil 5’-monophosphate in Tetrahymena pyriformis. J Biol Chem 239: 1177–1187PubMedGoogle Scholar
  20. Izzo P, Traboni C, Esposito F, Salvatore F, Cimino F (1979) Transfer RNA methylation in normal and transformed chick embryo fibroblasts. Special FEBS Meeting on Enzymes, Dubrovnik-Cavtat, YugoslaviaGoogle Scholar
  21. Karle JM, Anderson LW, Dietrick DD, Cysyk RL (1980) Determination of serum and plasma uridine levels in mice, rats, and humans by high pressure liquid chromatography. Anal Biochem 109: 41–46PubMedCrossRefGoogle Scholar
  22. Katze JR (1975) Relation of cell type and cell density to the degree of posttranscriptional modification of tRNALys and tRNAphe. Biochim Biophys Acta 407:392–398PubMedGoogle Scholar
  23. Katze JR (1978) Relation of cell type and cell density in tissue culture to the isoaccepting spectra of the nucleoside Q containing tRNAs: tRNATyr, tRNAHys, tRNAAsn, tRNAAsp. Nucleic Acids Res 5:2513–2524PubMedCrossRefGoogle Scholar
  24. Kerr SJ (1978) tRNA methyltransferase. In: Busch H (ed) Methods Cancer Res 15:163–185Google Scholar
  25. Koller CA, Stetson PL, Nichamin LV, Mitchell BS (1980) An essay of deoxyadenosine and adenosine in human plasma by HPLC. Biochem Med 24: 179–184PubMedCrossRefGoogle Scholar
  26. Kuchino Y, Borek E (1978) Tumour-specific phenylalanine tRNA contains two supernumerary methylated bases. Nature 271:126–129PubMedCrossRefGoogle Scholar
  27. Lakings DB, Waalkes TP, Borek E, Gehrke CW, Mrochek JE, Longmore J, Adamson RH (1977) Composition, associated tissue methyltransferase activity, and catabolic end products of transfer RNA from carcinogen-induced hepatoma and normal monkey livers. Cancer Res 37:285–292PubMedGoogle Scholar
  28. Levine L, Waalkes TP, Stolbach L (1975) Serum levels of N2,N2dimethylguanosine and pseudouridine as determined by radioimmunoassay for patients with malignancy. J Natl Cancer Inst 54:341–343PubMedGoogle Scholar
  29. Littauer UZ, Inouye H (1973) Regulation of tRNA. Ann Rev Biochem 42:439–470PubMedCrossRefGoogle Scholar
  30. Matsushita T, Davis FF (1971) Studies on pseudouridylic acid synthetase from various sources. Biochim Biophys Acta 238: 165–173PubMedGoogle Scholar
  31. Nishimura S (1979) Modified nucleosides in tRNA. In: Schimmel PR, Söll D, Abelson JN (eds) Transfer RNA: Structure, properties and recognition. Cold Spring Harbor Laboratory, pp 59–79Google Scholar
  32. Okada N, Shindo-Okada N, Sato S, Itoh YH, Oda KI, Nishimura S (1978) Detection of unique tRNA species in tumor tissues by Escherichia coli guanine insertion enzyme. Proc Natl Acad Sci USA 75: 4247–4251PubMedCrossRefGoogle Scholar
  33. Pergolizzi RG, Engelhardt DL, Grunberger D (1978) Formation of phenylalanine transfer RNA lacking the Wye base in VERO cells during methionine starvation. J Biol Chem 253:6341–6343PubMedGoogle Scholar
  34. Pfadenhauer EH, Sun-de Tong (1979) Determination of inosine and adenosine in human plasma using high-performance liquid chromatography and a boronate affinity gel. J Chromatogr 162:585–590PubMedCrossRefGoogle Scholar
  35. Pierré A, Berneman A, Vedel M, Robert-Géro M, Vigier P (1978) Avian oncornavirus associated INP-methylguanine transferase, location and origin. Biochem Biophys Res Comm 81:315–321PubMedCrossRefGoogle Scholar
  36. Raba M, Limburg K, Burghagen M, Katze JR, Simsek M, Heckman JE, Rajbhandary UL, Gross HJ (1979) Nucleotide sequence of three isoaccepting lysine tRNAs from rabbit liver and SV40-transformed mouse fibroblasts. Eur J Biochem 97: 305–318PubMedCrossRefGoogle Scholar
  37. Randerath E, Gopalakrishnan AS, Gupta RC, Agrawal HP, Randerath K (1981) Lack of a specific ribose methylation at guanosine 17 in Morris hepatoma 5123 D tRNAIGASer1. Cancer Res 41:2863–2867PubMedGoogle Scholar
  38. Rappaport H (1966) Tumors of hematopoietic system, Atlas of tumor pathology, sec III, fasc 8. Washington DC, Armed Forces Institute of PathologyGoogle Scholar
  39. Robert-Géro M, Lawrence F, Farrugia G, Berneman A, Blanchard P, Vigier P, Lederer E (1975) Inhibition of virus-induced cell transformation by synthetic analogues of S-adeno-sylhomocysteine. Biochem Biophys Res Comm 65: 1242–1249PubMedCrossRefGoogle Scholar
  40. Roe BA, Stankiewicz AF, Rizi HL, Weisz C, Di Lauro MN, Pike D, Chen CY, Chen EY (1979) Comparison of rat liver and Walker 256 carcinosarcoma tRNAs. Nucleic Acids Res 6:673–688PubMedCrossRefGoogle Scholar
  41. Russo T, Colonna A, Esposito F, Salvatore F, Cimino F (1982) Detection and estimation of several modified nucleosides in serum of cancer patients. Ital J Biochem 31:75–78Google Scholar
  42. Salomon R, Giveon D, Kimhi Y, Littauer UZ (1976) Abundance of tRNAPhe lacking the peroxy Y-base in mouse neuroblastoma. Biochemistry 15: 5258–5262PubMedCrossRefGoogle Scholar
  43. Salvatore F, Izzo P, Traboni C, Esposito F, Cimino F (1982) Studies of transfer RNA methylation in cell transformation. In: Usdin E, Borchardt RT, Creveling CR (eds) Biochemistry of S-Adenosyl-methionine and related compounds. MacMillan, London, pp 389–397Google Scholar
  44. Shindo-Okada N, Terada M, Nishimura S (1981) Changes in amount of hypo-modified tRNA having guanine in place of Queuine during erythroid differentiation of murine erythroleu-kemia cells. Eur J Biochem 115: 423–428PubMedCrossRefGoogle Scholar
  45. Silbert DF, Fink GR, Ames BN (1966) Histidine regulatory mutants in Salmonella typhimurium-III. A class of regulatory mutants deficient in tRNA for histidine. J Mol Biol 22:335–347PubMedCrossRefGoogle Scholar
  46. Speer J, Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) tRNA breakdown products as markers for cancer. Cancer 44: 2120–2123PubMedCrossRefGoogle Scholar
  47. Sueoka N, Kano-Sueoka T (1970) Transfer RNA and cell differentiation. Prog Nucleic Acid Res Mol Biol 10: 23–55PubMedCrossRefGoogle Scholar
  48. Suzuki T, Hochster RM (1966) On the biosynthesis of pseudouridine and of pseudouridylic acid in Agrobacterium tumefaciens. Can J Microbiol 44: 259–272Google Scholar
  49. Tormey DC, Waalkes TP, Ahmann D, Gehrke CW, Zumwalt RW, Snyder J, Hansen H (1975) Biological markers in breast carcinoma I. Incidence of abnormalities of CEA, HCG, three polyamines, and three minor nucleosides. Cancer 35: 1095–1100PubMedCrossRefGoogle Scholar
  50. Tormey DC, Waalkes TP, Gehrke CW (1980) Biological markers in breast carcinoma. Clinical correlations with pseudouridine, N2,N2-dimethylguanosine, and 1-methylinosine. J Surg Oncol 14:267–273PubMedCrossRefGoogle Scholar
  51. Vedel M, Robert-Gèro M, Legraverend M, Lawrence F, Lederer E (1978) Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5’deoxy 5’-S-isobutyladenosine (SIBA). Nucleic Acids Res 5:2979–2989PubMedCrossRefGoogle Scholar
  52. Waalkes TP, Borek E (1975) The biochemical assessment of the malignant status in man: Aspects related to tRNA modification. In: Biological characterization of human tumours (6th International Symposium). Excerpta Medica, Amsterdam pp 15–31Google Scholar
  53. Waalkes TP, Gehrke CW, Zumwalt RW, Chang SY, Lakings DB, Tormey DC, Ahmann DL, Moertel CG (1975) The urinary excretion of nucleosides of ribonucleic acid by patients with advanced cancer. Cancer 36: 390–398PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin • Heidelberg 1983

Authors and Affiliations

  • F. Salvatore
    • 1
  • A. Colonna
    • 1
  • F. Costanzo
    • 1
  • T. Russo
    • 1
  • F. Esposito
    • 1
  • F. Cimino
    • 1
  1. 1.Istituto di Chimica Biologica, II Facoltà di Medicina e ChirurgiaUniversità di NapoliNapoliItaly

Personalised recommendations