Table Of ContentRecent Results 84
in Cancer Research
Fortschritte der Krebsforschung
Progres dans les recherches sur Ie cancer
Editor in Chief: P. Rentchnick, Geneve
Co-editor: H. J. Senn, St. Gallen
Modified
Nucleosides
and Cancer
Edited by Gisela N ass
With 217 Figures and 89 Tables
Springer-Verlag
Berlin Heidelberg New York 1983
Professor Dr. Gisela N ass
Zentrallaboratorium rur Mutagenitatspriifung
der Deutschen Forschungsgemeinschaft
Breisacher Strasse 33, D-7800 Freiburg, FRG
Sponsored by the Swiss League against Cancer
ISBN-13: 978-3-642-81949-0 e-ISBN-13: 978-3-642-81947-6
001: 10.1007/978-3-642-81947-6
Library of Congress Cataloging in Publication Data. Main entry under title: Modified
nucleosides and cancer. (Recent results in cancer research - Fortschritte der Krebs
forschung - Progres dans les r'echerches sur Ie cancer; 84) Bibliography: p. Includes
index. 1. Nucleosides-Metabolism. 2. Cancer. 1. Nass, Gisela. II. Series: Recent results
in cancer research; 84. [DNLM: 1. Nucleosides-Metabolism. 2. Neoplasms-Metabolism.
WI REI06P v.84/QZ 200 M692] RC261.R35 vol. 84 616.99'4s 82-19320
[QP625.N88] [616.99'4'00154779]
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Preface
This book comprises the lectures presented at the workshop
Modified Nuc1eosides and Cancer held from 28 September to
2 October, 1981 in Freiburg, West Germany. The workshop
was organized by Gisela Nass and sponsored by the Deutsche
Forschungsgemeinschaft.
The purpose of the workshop was to cover the varied analytical
methods for quantitative and qualitative determination of
modified nucleosides and their metabolism including bio
synthesis, all in relation to the function of these compounds
in the origin and growth of cancer cells. The potential signi
ficance of measuring modified nucleosides in body fluids for
tumor diagnosis in humans received particular attention.
Various fields of research which have previously been segregat
ed are thus unified in this volume.
Emphasis was also placed on the fact that modified nucleosides
are constituents of the genetic material, the desoxyribonucleic
acid, on the one hand, and of the transfer ribonucleic acids
>
on the other hand, with the latter macromolecules participating
not only in the translation of genetic information into protein,
but also in many regulatory processes in all single- and multi-
, cellular organisms including man.
Sincere thanks are due to Roswitha Hilden for her skillful
help in organizing the workshop, as well as to Rainer Diesel
and Dr. Gabor Igloi for their invaluable assistance in the
editorial work of this volume.
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
S. Sharp, L. Cooley, D. DeFranco, T. Dingermann, and
D.Soll:
Organization and Expression of tRNA Genes in
Drosophila Melanogaster ....................... 1
G. Dirheimer:
Chemical Nature, Properties, Location, and Physiological
and Pathological Variations of Modified Nucleosides
intRNAs ................................... 15
Session I. Modified Nucleosides in Situ in Tumors and
Transformed Cells of Cell Culture ................ 47
InDNA .................................... 49
A.E.Pegg:
Formation and Removal of Methylated Nucleosides in
Nucleic Acids of Mammalian Cells ................ 49
M. F. Rajewsky:
Structural Modifications and Repair of DNA in Neuro-
OncogenesisbyN-Ethyl-N-nitrosourea ............ 63
H.-G. Neumann:
Role of Extent and Persistence of DNA Modifications
in Chemical Carcinogenesis by Aromatic Amines 77
L. Vardimon, D. Renz, and W. Doerfler:
Can DNA Methylation Regulate Gene Expression? 90
VIII Contents
IntRNA 103
K. Randerath, H. P. Agrawal, and E. Randerath:
tRNA Alterations in Cancer ..................... 103
1. F. Mushinski and M. Marini:
Tumor-Specific tRNA Modifications in Mouse
Plasmacytomas and Other Tumors ................ 121
D. Grunberger, R. G. Pergolizzi, Y. Kuchino,
1. F. Mushinski, and S. Nishimura:
Alterations in Post-Transcriptional Modification of the
Y Base in Phenylalanine tRNA from Tumor Cells ..... 133
1. R. Katze, W. T. Beck, C. S. Cheng, and 1. A McCloskey:
Why Is Tumor tRNA Hypomodified with Respect to
QNucleoside? ............................... 146
B.l. Ortwerth and V. K. Lin:
The Effects of Growth Factors on tRNALys Modification 160
C. Hedgcoth, K. Hayenga, K. Scheets, K. R. Thomas,
M. Harrison, V. K. Lin, and B. 1. Ortwerth:
Perturbation of the Mitochondrial Lysine tRNA
Population by Virus-Induced Transformation or Stress of
Mammalian Cells: Functional Properties and Nucleotide
Sequence of a Mitochondrially Associated Lysine tRNA 171
S. Litvak, L. Sarih, M. Fournier, F. von der Haar,
B. Labouesse, and A Araya:
Involvement of tRNA in Retrovirus Expression:
Biological Implications of Reverse Transcriptase-Primer
.. tRNAInteractions . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 184
Session II. Biosynthesis and Degradation
of Modified N ncleosides in Cancer Cells ............ 191
DNA-SpeciJicEnzyines . . . . . . . . . . . . . . . . . . . . . . . .. 193
A Pfohl-Leszkowicz, R. P. P. Fuchs, G. Keith, and
G. Dirheimer:
Enzymatic Methylation of Chicken Erythrocyte DNA
Modified by Two Carcinogens,
2-(N-Acetoxyacetylamino) Fluorene and
Methylnitrosourea . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 193
P.A.lones, S.M. Taylor, and v.L. Wilson:
Inhibition of DNA Methylation by 5-Azacytidine ..... 202
T. L. 1. Boehm and D. Drahovsky:
Alteration of Enzymatic DNA Methylation by Chemical
Carcinogens ................................. 212
Contents IX
tRNA-SpecijicEnzymes 226
S.l.Kerr:
Ethionine-Induced Alterations oftRNA Metabolism .. 226
P. F. Agris, T. Playl, L. Goldman, E. Horton,
D. Woolverton, D. Setzer, and C. Rodi:
Processing of tRNA Is Accomplished by a High-
Molecular-Weight Enzyme Complex ............ . .. 237
H.Kersten:
Alteration of tRNA Modification in Eukaryotes: Causes
and Consequences ............................. 255
A. M. Leyman, P. Goddeeris, l. M. Lauwerijns, and
W. De Loecker:
Effects of Cortisol on tRNA Methylase Activities in Rat
Mammary Carcinoma .......................... 264
B. B. Goswami, O. K. Sharma, and E. Borek:
An Approach to Inhibition of Viral Replication:
Inhibition of mRNA Methylation ................. 275
K. Randerath, W.-c. Tseng, l. S. Harris, and L.-l. W. Lu:
Specific Effects of 5-Fluoropyrimidines and
5-Azapyrimidines on Modification of the 5 Position of
Pyrimidines, in Particular the Synthesis of 5-Methyluracil
and 5-Methylcytosine in Nucleic Acids ............. 283
Session III. Modified NucIeosides: Type and
Concentration in Body Fluids and Relevance for Cancer
Therapy of Tumor-Bearing Individuals ............. 299
E.Borek, O.K.Sharma, and T.P. Waalkes:
New Applications of Urinary Nucleoside Markers 301
l. Muller, N. Erb, G. Heller-Schoch, H. Lorenz,
K. Winkler, and G. Schoch:
Multivariate Analysis of Urinary RNA Catabolites in
, Malignancies: Cross-Sectional and Longitudinal Studies 317
T. Rasmuson, G. R. Bjork, L. Damber, S. E. Holm,
L. 1a cobsson, A. 1 eppsson, B. Littbrand, T. Stigbrand,
and G. Westman:
Evaluation of Carcinoembryonic Antigen, Tissue
Polypeptide Antigen, Placental Alkaline Phosphatase,
and Modified Nucleosides as Biological Markers in
Malignant Lymphomas ......................... 331
x
Contents
c.
W. Gehrke, R. W. Zumwalt, R.A. McCune,
and K. C. Kuo:
Quantitative High-performance Liquid Chromatography
Analysis of Modified Nuc1eosides in Physiological Fluids,
tRNA, and DNA ............................. 344
F. Salvatore, A. Colonna, F. Costanzo, T. Russo,
F. Esposito, and F. Cimino:
Modified Nuc1eosides in Body Fluids of Tumor-Bearing
Patients .................................... 360
1. Thomale and G. Nass:
Increasing Urinary Levels of Modified Nuc1eosides and
Bases During Tumor Development in Mice ......... 378
I. Clark, 1. W. MacKenzie, 1. R. McCoy, and W. Lin:
Comparison of Urinary Modified Nuc1eosides and Bases
in Rats with Hepatoplas and Nephroblastomas ....... 388
S. Nishimura, N. Shindo-Okada, H. Kasai, Y. Kuchino,
S. Noguchi, M.ligo, and A. Hoshi:
Characterization and Analysis of Oncofetal tRNA and
Its Possible Application for Cancer Diagnosis and
Therapy .................................... 401
M. Mach, U. Schneider, and W. Kersten:
Excretion of Polyamines by Children with Leukemia
During Chemotherapy ......................... 413
Subject Index 421
List of Authors*
Agrawal, H.P. 1031 Harris, J. S. 283
Agris, P.F. 237 Harrison, M. 171
Araya, A. 184 Hayenga, K 171
Beck, W.T. 146 Hedgcoth, C. 171
Bjork, G.R. 331 Heller-Schoch, G. 317
Boehm, T.L.J. 212 Holm, S.E. 331
Borek, E. 275, 301 Horton, E. 237
Cheng, C. S. 146 Hoshi, A. 401
Cimino, F. 360 Iigo, M. 401
Clark,L 388 Jacobsson, L. 331
Colonna, A. 360 Jeppsson, A. 331
Cooley, L. 1 Jones, P.A. 202
Costanzo, F. 360 Kasai, H. 401
Damber, L. 331 Katze, J.R. 146
DeFranco, D. 1 Keith, G. 193
DeLoecker, W. 264 Kerr, S.J. 226
Dingermann, T. 1 Kersten, H. 255
Dirheimer, G. 15,193 Kersten, W. 413
Doerfler, W. 90 Kuchino, Y. 133,401
Drahovsky, D. 212 Kuo, KC. 344
Erb, N. 317 Labouesse, B. 184
Esposito, F. 360 Lauwerijns, J.M. 264
Fournier, M. 184 Leyman, A. M. 264
Fuchs, R.P.P. 193 Lin, V.K 160,171
Gehrke, C.W. 344 Lin, W. 388
Goddeeris, P. 264 Littbrand, B: 331
Goldman, L. 237 Litvak, S. 184
Goswami, B.B. 275 Lorenz, H. 317
Grunberger, D. 133 Lu, L.-J. W. 283
Haar, F. von der 184 Mach,M. 413
* The address of each mentioned authors is indicated below the
according contribution heading
1 Page, on which contribution commences
XII List of Authors
MacKenzie,J.W. 388 Salvatore, F. 360
Marini, M. 121 Sarih, L. 184
McCloskey, J.A 146 Scheets, K. 171
McCoy, J.R. 388 Schneider, U. 413
McCune, R. A 344 Schoch, G. 317
MiilIer, J. 317 Setzer, D. 237
Mushinski, J.F. 121,133 Sharma, O.K. 275,301
Nass, G. 378 Sharp, S. 1
Neumann, H.-G. 77 Shindo-Okada, N. 401
Nishimura, S. 133,401 SolI, D. 1
Noguchi, S. 401 Stigbrand, T. 331
Ortwerth, B. J. 160, 171 Taylor, S.M. 202
Pegg, AE. 49 Thomale, J. 378
Pergolizzi, R. G. 133 Thomas, K.R. 171
Pfohl-Leszkowicz, A 193 Tseng, W. 283
Playl, T. 237 Vardimon, L. 90
Rajewsky, M.F. ,:63 Waalkes, T.P. 301
Randerath, E. 103 Westman, G. 331
Randerath, K. 103,283 Wilson, V.L. 202
Rasmuson, T. 331 Winkler, K. 317
Renz, D. 90 Woolverton, D. 237
Rodi, C. 237 Zumwalt, R. W. 344
Russo, T. 360
