Skip to main content
SpringerLink
Log in

Modified Nucleosides in Body Fluids of Tumor-Bearing Patients

  • Chapter
Modified Nucleosides and Cancer

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).

Work in the authors’ laboratory has been supported by research grants from the National Research Council, Rome: Progetto Finalizzato Controllo Crescita Neoplastica. The authors wish to thank Dr. C. W. Gehrke, University of Missouri, Columbia, MO, USA, for making available his unpublished results on HPLC methodology for estimation of nucleosides in body fluids

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

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

m 22 G:

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

m 22 Gua:

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

References

  • Agris PF (1980) The modified nucleosides in tRNA. Liss, New York

    Google Scholar 

  • Borek E, Kerr SJ (1972) Atypical transfer RNA’s and their origin in neoplastic cells. Adv Cancer Res 15:163–190

    Article  PubMed  CAS  Google Scholar 

  • 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: 3362–3366

    PubMed  CAS  Google Scholar 

  • 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 457–464

    Google Scholar 

  • 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 40:417–423

    PubMed  CAS  Google Scholar 

  • Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31: 1860–1861

    PubMed  CAS  Google Scholar 

  • Chambers RW (1966) The Chemistry of pseudouridine. Prog Nucleic Acid Res Mol Biol 5:349–398

    Article  PubMed  CAS  Google Scholar 

  • 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–113

    Google Scholar 

  • 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 409–412

    Google Scholar 

  • 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 330

    Google Scholar 

  • 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: 640

    Google Scholar 

  • 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: 1427–1435

    PubMed  CAS  Google Scholar 

  • 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 19–41

    Google Scholar 

  • 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 150:455–476

    Article  CAS  Google Scholar 

  • Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) Patterns of urinary excretion of modified nucleosides. Cancer Res 39: 1150–1153

    PubMed  CAS  Google Scholar 

  • 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, France

    Google Scholar 

  • Grunberger D, Weinstein IB (1975) Deficiency of the Y base in a hepatoma phenylalanine tRNA. Nature 253:66–67

    Article  PubMed  CAS  Google Scholar 

  • 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: 659–676

    Article  PubMed  CAS  Google Scholar 

  • Heinrikson RL, Goldwasser E (1964) Studies on the biosynthesis of 5-ribosyluracil 5’-monophosphate in Tetrahymena pyriformis. J Biol Chem 239: 1177–1187

    PubMed  CAS  Google Scholar 

  • 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, Yugoslavia

    Google Scholar 

  • 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: 41–46

    Article  PubMed  CAS  Google Scholar 

  • Katze JR (1975) Relation of cell type and cell density to the degree of posttranscriptional modification of tRNALys and tRNAphe. Biochim Biophys Acta 407:392–398

    PubMed  CAS  Google Scholar 

  • 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 5:2513–2524

    Article  PubMed  CAS  Google Scholar 

  • Kerr SJ (1978) tRNA methyltransferase. In: Busch H (ed) Methods Cancer Res 15:163–185

    Google Scholar 

  • Koller CA, Stetson PL, Nichamin LV, Mitchell BS (1980) An essay of deoxyadenosine and adenosine in human plasma by HPLC. Biochem Med 24: 179–184

    Article  PubMed  CAS  Google Scholar 

  • Kuchino Y, Borek E (1978) Tumour-specific phenylalanine tRNA contains two supernumerary methylated bases. Nature 271:126–129

    Article  PubMed  CAS  Google Scholar 

  • 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 37:285–292

    PubMed  CAS  Google Scholar 

  • 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 54:341–343

    PubMed  CAS  Google Scholar 

  • Littauer UZ, Inouye H (1973) Regulation of tRNA. Ann Rev Biochem 42:439–470

    Article  PubMed  CAS  Google Scholar 

  • Matsushita T, Davis FF (1971) Studies on pseudouridylic acid synthetase from various sources. Biochim Biophys Acta 238: 165–173

    PubMed  CAS  Google Scholar 

  • 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 59–79

    Google Scholar 

  • 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: 4247–4251

    Article  PubMed  CAS  Google Scholar 

  • 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 253:6341–6343

    PubMed  CAS  Google Scholar 

  • 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 162:585–590

    Article  PubMed  CAS  Google Scholar 

  • 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 81:315–321

    Article  PubMed  Google Scholar 

  • 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: 305–318

    Article  PubMed  CAS  Google Scholar 

  • 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 41:2863–2867

    PubMed  CAS  Google Scholar 

  • Rappaport H (1966) Tumors of hematopoietic system, Atlas of tumor pathology, sec III, fasc 8. Washington DC, Armed Forces Institute of Pathology

    Google Scholar 

  • 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: 1242–1249

    Article  PubMed  Google Scholar 

  • 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 6:673–688

    Article  PubMed  CAS  Google Scholar 

  • 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 31:75–78

    Google Scholar 

  • Salomon R, Giveon D, Kimhi Y, Littauer UZ (1976) Abundance of tRNAPhe lacking the peroxy Y-base in mouse neuroblastoma. Biochemistry 15: 5258–5262

    Article  PubMed  CAS  Google Scholar 

  • 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 389–397

    Google Scholar 

  • 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: 423–428

    Article  PubMed  CAS  Google Scholar 

  • 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 22:335–347

    Article  PubMed  CAS  Google Scholar 

  • Speer J, Gehrke CW, Kuo KC, Waalkes TP, Borek E (1979) tRNA breakdown products as markers for cancer. Cancer 44: 2120–2123

    Article  PubMed  CAS  Google Scholar 

  • Sueoka N, Kano-Sueoka T (1970) Transfer RNA and cell differentiation. Prog Nucleic Acid Res Mol Biol 10: 23–55

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Hochster RM (1966) On the biosynthesis of pseudouridine and of pseudouridylic acid in Agrobacterium tumefaciens. Can J Microbiol 44: 259–272

    CAS  Google Scholar 

  • 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: 1095–1100

    Article  PubMed  CAS  Google Scholar 

  • 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 14:267–273

    Article  PubMed  CAS  Google Scholar 

  • 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 5:2979–2989

    Article  PubMed  CAS  Google Scholar 

  • 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 15–31

    Google Scholar 

  • 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: 390–398

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Chimica Biologica, II Facoltà di Medicina e Chirurgia, Università di Napoli, Via S. Pansini 5, 80131, Napoli, Italy

    F. Salvatore, A. Colonna, F. Costanzo, T. Russo, F. Esposito & F. Cimino

Authors
  1. F. Salvatore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Colonna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Costanzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Cimino
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zentrallaboratorium für Mutagenitätsprüfung, Deutschen Forschungsgemeinschaft, Breisacher Strasse 33, D-7800, Freiburg, Germany

    Gisela Nass

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Springer-Verlag Berlin • Heidelberg

About this chapter

Cite this chapter

Salvatore, F., Colonna, A., Costanzo, F., Russo, T., Esposito, F., Cimino, F. (1983). Modified Nucleosides in Body Fluids of Tumor-Bearing Patients. In: Nass, G. (eds) Modified Nucleosides and Cancer. Recent Results in Cancer Research/Fortschritte der Krebsforschung/Progrès dans les recherches sur Ie cancer, vol 84. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81947-6_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-81947-6_27

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-81949-0

  • Online ISBN: 978-3-642-81947-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation