Summary
Unfractionated t-RNAs from brain tumours contain higher amounts of methylated bases and 2′-O-riboses, compared to normal human brain; the methylated base ratios are significantly altered. The secondary structure of the tumoural t-RNAs differs, mainly in relation to the base pairing. An hypothetical schema of the role of the modifications of the primary and secondary structures of the t-RNA in the metabolism of the tumour cell is proposed. It is assumed that a loss of specificity of the methylase activities occurs in brain tumours.
Zusammenfassung
Unfraktionierte t-RNS von Hirntumoren enthalten mehr methylierte Basen und 2′-O-Ribosen als das normale menschliche Hirngewebe. Das Verhältnis der methylierten Basen zueinander ist bedeutsam verändert. Die Sekundärstruktur der tumoralen t-RNS variiert hauptsächlich in Abhängigkeit von der Basenpaarung. In einem hypothetischen Schema wird dargelegt, welche Rolle die Veränderungen der Primär- und Sekundärstrukturen der t-RNS im Stoffwechsel der Tumorzellen spielen. Man nimmt an, daß in Hirntumoren ein Spezifizitätsverlust der Methylaseaktivität vorliegt.
Résumé
Les acides ribonucléiques de transfert non fractionnés, provenant de tumeurs cérébrales, sont plus riches en bases et en riboses 2′-O-méthylés, par comparaison avec ceux du tissu cérébral humain normal;les rapports des bases méthylées entre elles sont modifiés de façon significative. La structure secondaire des ARN de transfert des tumeurs diffère, surtout au niveau des interactions base-base. Un schéma hypothétique du rôle que les modifications des structures primaires et secondaires de l'ARN de transfert joue dans le métabolisme des tumeurs est exposé. On admet qu'il existe une perte de spécificité des activités méthylasiques dans certaines tumeurs cérébrales.
Riassunto
t-ARN non frazionati di tumori cerebrali contengono quantità maggiori di basi e 2′-O-ribosi metilati, ripsetto al cervello umano normale; i rapporti fra le basi metilate sono significativamente alterati. La struttura secondaria dei t-ARN tumorali differisce, in rapporto soprattutto con gli aecoppiamenti delle basi. Uno schema ipotetico del ruolo svolto dalle modificazioni a carico delle strutture primaria e secondaria dei t-ARN nel metabolismo tumorale é esposto. Si ammette ehe una perdita di specificità delle reazioni metilasiche ricorre in certi tumori cerebrali.
Resumen
Los t-ARN no fraccionados de los tumores cerebrales son más ricos en bases y 2′-O-riboses metiladas, en comparación con el cerebro humano normal; las relaciones entre las bases metiladas estan alteradas muy significativamente. La estructura seoundaria de las t-ARN de los tumores difiere en relación, sobre todo, con las interacciones base-base. Se expone un esquema hipotético del papel que las modificaciones de las estructuras primaria y secundaria del t-ARN juegan en el metabolismo de los tumores. Se admite una pérdida de especificidad de las actividades metilásicas en ciertos tumores cerebrales.
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References
Baguley, B. C., andN. Staehelin, Substrate specificity of adenine-specific transfer RNA methylase in normal and leukemic tissues. Europ. J. Biochem.6 (1968), 1–7.
Baldessarini, R. J., andP. P. Carbone, Adenosylmethionine elevation in leukaemic white blood cells. Science149 (1963), 644–645.
Baliga, B., P. R. Srinivasan, andE. Borek, Changes in the t-RNA methylating enzymes during insect metamorphosis. Nature208 (1965), 555–557.
Bergquist, P. L., andR. E. F. Matthews, Distribution of methylated purines in cell fractions from mouse liver and tumor. Biochim. Biophys. Acta34 (1959), 567–569.
— —, Occurrence and distribution of methylated purines in the ribonucleic acids of subcellular fractions. Biochem. J.85 (1962), 305–313.
Blunk, J. M., andP. E. Hughes, An investigation of possible transfer of 5-methyl groups to the amino nitrogen of aminoazo dyes. Oncology22 (1968), 118–128.
Borek, E., The methylation of transfer RNA; mechanism and function. Cold Spring Harbor Symp. Quant. Biol.28 (1963), 139–148.
—,L. K. Mandel, andE. Fleissner, The origin of the methylated bases in RNA. Federation Proc.21 (1962), 379.
—, andP. R. Srinivasan, Alteration of the macromolecular structure of nucleic acids by transmethylation. In:S. K. Shapiro, andF. Schlenk, Transmethylation and methionine biosynthesis. Chicago-London: Univ. of Chicago Press. 1966.
Brown, G. L., Preparation, fractioning and properties of s-RNA. In:Davidson, J. N., andW. E. Cohn, Progress in nucleic acid research and molecular biology, vol. 2. New York-London: Academic Press. 1963.
Cantoni, G. L., Molecular architecture of s-RNA. In:T. Hayashi andA. G. Szent-Györgyi, Molecular architecture in cell physiology. Englewood Cliffs: Prentice-Hall. 1964.
—,H. Richards, andK. Tanaka, A coding function of the methylated bases in s-RNA. Federation Proc.22 (1963), 230.
Capra, J. O., andA. Peterkofsky, A difference between “normal” and “methyldeficient” Escherichia c. s-RNA in polynucleotide-directed binding of leucyl-s-RNA to ribosomes. Fed. Proc.25 (1966), 403.
Comb, D. G., Methylation of nucleic acids during sea-urchin embryo development. J. Mol. Biol.11 (1965), 851–855.
Farber, E., Biochemistry of carcinogenesis. Cancer Res.28 (1968), 1859–1869.
Gold, M., andJ. Hurwitz, Enzymatic methylation of nucleic acids. Fed. Proc.22 (1963), 230.
Gros, P. R., L. I. Malkin, andW. A. Moyer, Templates for the first proteins of embryonic development. In:E. Bell, Molecular and cellular aspects of development. New York-Evanston-London: Harper and Row. 1967.
Hancock, R. L., Utilization of L-Methionine and S-Adenosyl-L-Methionine for Methylation of soluble RNA by mouse liver and Hepatoma Extracts. Cancer Res.27 (1967), 646–653.
Hartman, K. A., The infrared spectra of some complexes of metal ions with nucleosides and nucleotides. Biochim. Biophys. Acta138 (1967), 192–195.
Heilporn-Pohl, V., S. Limbosch-Rolin, andJ. Quertier, Effects of mercaptoethanol on the methylation of ribonucleic acids. Biochim. Biophys. Acta134 (1967), 191–194.
Heinmets, F., Analysis of normal and abnormal cell growth. New York: Plenum Press. 1966.
Herrmann, H., Quantitative studies of protein synthesis in some embryonic tissues. In:M. Locke, Cytodifferentiation and macromolecular synthesis. New York-London: Academic Press. 1963.
Holley, R. W., J. Apgar, G. A. Everett, J. T. Madison, M. Marquisel, S. H. Merrill, J. R. Penswick, andA. Zamir, Structure of a ribonucleic acid. Science147 (1965), 1462–1465.
Hurwitz, J., andM. Gold, t-RNA methylase from Escherichia coli. In:G. L. Cantoni, andD. R. Davies, Procedures in nucleic acid research. New York-London: Harper and Row. 1966.
Kaye, A. M., andP. S. Leboy, Methylation of RNA by mouse organs and tumors: ionic stimulation in vitro. Biochim. Biophys. Acta157 (1968), 289–302.
Kyogoku, Y., M. Tsuboi, T. Shimanouchi, andI. Watanabe, Nucleic acids in deuterium oxide solution. Nature189 (1961), 120–122.
— — — —, Infrared spectra of formamide—treated nucleic acids. J. Mol. Biol.3 (1961), 741–745.
— — — —, Proton transfer in nucleic acids. Nature195 (1962), 460–462.
Landin, R. M., etY. Moulé, Particularités de renouvellement du RNA soluble in vivo dans le foie du rat. Biochim. Biophys. Acta129 (1966), 249–258.
Lawley, P. D., Effects of alkylating agents on nucleic acids and their relation to other mutagens. In: Anderson Hosp. Ed., The molecular basis of neoplasia. Austin: Univ. of Texas Press. 1962.
—, Effects of some chemical mutagens and carcinogens on nucleic acids. In:J. N. Davidson, andW. E. Cohn, Progress in nucleic acid research and molecular biology, Vol. 5. New York-London: Academic Press. 1966.
—, andP. Brookes, Further studies on the alkylation of nucleic acids and their constituent nucleotides. Biochem. J.89 (1963), 127–138.
— —,P. N. Magee, V. M. Craddock, andP. F. Swann, Methylated bases in liver nucleic acids from rats treated with dimethylnitrosamine. Biochim. Biophys. Acta157 (1968), 646–648.
Lin, J. K., J. A. Miller, andE. C. Miller, On the structure of the hepatic protein-bound derivatives of N-methyl-4-amino-azobenzene (MAB) in the rat. Proc. Amer. Ass. Cancer Res.8 (1967), 41.
Louisot, P., L. Colobert, C. Bollack, J. H. Weil etJ. P. Ebel, Inhibition de la multiplication virale à l'aide d'acides ribonucleiques chimiquement modifiés. I. Inhibition de la multiplication de myxovirus parainfluenzal I (Virus Sendai) sur cellules de rein de veau. Biochim. Biophys. Acta155 (1968), 38–50.
Ludlum, D. B., Alkylation of synthetic polynucleotides. Proc. Amer. Ass. Cancer Res.7 (1966), 44.
—, Methylation and secondary structure of polyadenylic acid. Biochim. Biophys. Acta119 (1966), 630–633.
—,R. C. Warner, andA. Y. Wahabe, Alkylation of synthetic polynucleotides. Science145 (1964), 397–399.
Madison, J. T., G. A. Everett, andH. Kung, Nucleotide sequence of a yeast tyrosine transfer RNA. Science153 (1966), 531–534.
Magee, R. N., Cellular injury and chemical carcinogenesis. In:R. W. Raven, Cancer Progress. London: Butterworth. 1963.
—, Interaction of chemical carcinogenesis with protein and nucleic acids. In:O. Mühlbock, andP. Emmelot, Cellular control mechanisms and cancer. Amsterdam: Elsevier. 1964.
—, andE. Farber, Toxic liver injury and carcinogenesis. Methylation of rat liver nucleic acids by dimethylnitrosamine in vivo. Biochem. J.83 (1962), 114–124.
—, andK. Y. Lee, Cellular injury and carcinogenesis. Alkylation of ribonucleic acid of rat liver by diethylnitrosamine and n-butylmethylnitrosamine in vivo. Biochem. J.91 (1964), 35–42.
—, andR. Schoental, Carcinogenesis by nitroso compounds. Brit. Med. Bull.20 (1964), 102–106.
Markert, C. L., Neoplasia: a disease of cell differentiation. Cancer Res.28 (1968), 1908–1914.
McCalla, D. R., Reaction of N-methyl-N′-nitro-N-nitroguanidine and N-methyl-N-nitroso-p-toluenesulfonamide with DNA in vitro. Biochim. Biophys. Acta155 (1968), 114–120.
Michelson, A. M., The chemistry of nucleosides and nucleotides. New York-London: Academic Press. 1963.
Miles, T. H., Proton transfer in nucleic acids. Nature195 (1962), 459–460.
—, Use of infrared spectroscopy for the measurement of nucleoside binding to polynucleotides. In:S. P. Colowick, andN. D. Kaplan (L. Grossman, andK. Moldave, Ed.), Methods in Enzymology, Vol. XII-B. New York-London: Academic Press. 1968.
Mittelman, A., R. H. Hall, D. S. Yohn, andJ. J. Grace, Jr., The in vitro soluble RNA methylase activity of SV 40 induced Hamster Tumors. Cancer Res.27 (1967), 1409–1414.
Miura, K. J., Specificity in the structure of transfer RNA. In:J. N. Davidson, andW. E. Cohn, Progress in nucleic acid research and molecular biology, Vol. 6. New York-London: Academic Press. 1967.
Muramatsu, M., andT. Fujisawa, Methylation of ribosomal RNA precursor and t-RNA in rat liver. Biochim. Biophys. Acta157 (1968), 476–492.
Nikolskaya, I. I., Z. G. Tkatcheva, B. F. Vanyushin, andT. I. Tikchonenko, On the presence of minor bases in DNA of phages DD 7 and Sd and their hosts. Biochim. Biophys. Acta155 (1968), 626–629.
Paul, J., Masking of genes in cytodifferentiation and carcinogenesis. In:A. V. S. De Reuck, andJ. Knight, Cell differentiation. London: Churchill. 1967.
Perria, L., eG. L. Viale, Una ipotesi sulla deviazione atipica nei gliomi. Acta Neurol.23 (1968), 612–614.
- - The RNA overmethylation in brain tumors. Data and hypothesis. Acta Neurochir. (in press).
Revel, M., andU. Z. Littauer, The coding properties of methyl deficient phenylalanine transfer RNA from Escherichia c. J. Mol. Biol.15 (1966), 389–394.
Sarkar, N., andD. G. Comb, Studies on the biosynthesis of transfer RNA. Fed. Proc.26 (1967), 734.
Scribner, J. D., J. A. Miller, andE. C. Miller, 3-methylmercapto-N-methyl-4-aminoazobenzene; an alkaline degradation product of a labile proteinbound dye in the livers of rats feed N,N-dimethyl-4-aminoazobenzene. Biochem. Biophys. Res. Comm.20 (1965), 560–565.
Shimanouchi, T., M. Tsuboi, T. Kyogoku, andJ. Watanabe, The 1680 cm-1 band of ribonucleic acid in D2O solution. Biochim. Biophys. Acta45 (1960), 195–196.
Shugart, L., G. D. Novelli, andP. M. Stulberg, Isolation and properties of undermethylated phenylalanine transfer ribonucleic acids from a relaxed mutant of Escherichia coli. Biochim. Biophys. Acta157 (1968), 83–90.
Silber, R., E. Bergman, B. Goldstein, H. Stein, G. Faruhan, andI. R. Bertino, Methylation of nucleic acids in normal and leukaemic leukocytes. Biochim. Biophys. Acta123 (1966), 638–640.
Simon, L. N., A. J. Glasky, andT. H. Rejal, Enzymes in the central nervous system. I. RNA methylase. Biochim. Biophys. Acta142 (1967), 99–104.
Smrt, J., J. Skoda, V. Lisy, andF. Sorm, Loss of coding properties of the trinucleotide guanylyl-uridylyl-uridine on replacement of urydylic acid by dihydro-urydilic acid. Biochim. Biophys. Acta129 (1966), 210–211.
Srinivasan, P. R., andE. Borek, Studies on the RNA methylases. Fed. Proc.23 (1964), 375.
— —, Enzymatic alteration of nucleic acid structure. Science145 (1964), 548–553.
— —, Enzymatic alteration of macromolecular structure. In:J. N. Davidson, andW. E. Cohn, Progress in nucleic acid research and molecular biology, Vol. 5. New York-London: Academic Press. 1966.
Starr, J. L., Functional capacity of “methyl-poor” amino acid transfer RNA. Fed. Proc.22 (1963), 230.
Strauss, B. S., andM. Robbins, DNA methylated in vitro by a monofunctional alkylating agent as a substrate for a specific nuclease from micrococcus lysodeikticus. Biochim. Biophys. Acta161 (1968), 68–75.
Trávnicěk, M., RNA with amino acid-acceptor activity isolated from an oncogenic virus. Biochim. Biophys. Acta166 (1968), 757–759.
Tsutsui, E., P. R. Srinivasan, andE. Borek, t-RNA methylases in tumors of animal and human origin. Proc. Nat. Acad. Science (Biochemistry)56 (1966), 1003–1009.
Viale, G. L., Histochemische Untersuchungen über die Cholinesterasen in Hirngeschwülsten. Acta Neuropath.2 (1962), 73–85.
—, Tecniche preparative e analitiche per lo studio degli acidi ribonucleici nei tumori del Sistema Nervoso. Riv. Neurobiol.13 (1967), 1116–1128.
Viale, G. L., Ricerche di spettrofotometria in infrarosso su t-RNA di giorni maligni. Riv. Neurobiol.14 (1968), 318–324.
—, undO. Candia, Embryonalkörnerschichten des Kleinhirns und Medulloblastom. Acta Neurochir.16 (1967), 267–269.
—, eA. Fondelli Restelli, Ricerche di spettrofotometria in infrarosso su t-RNA di tumori cerebrali. Tumori53 (1967), 323–329.
— —, eE. Viale, Basi metilate dei t-RNA dei tumori cerebrali. Tumori53 (1967), 533–539.
— — —, Nucleosidi metilati in t-RNA di tumori cerebrali. Sist. Nerv.20 (1968), 51–55.
— — —, Composizione in basi dei t-RNA dei gliomi. Riv. Neurobiol.14 (1968), 311–317.
Weinstein, I. B., A possible role of transfer RNA in the mechanism of carcinogenesis. Cancer Res.28 (1968), 1871–1874.
Wilhelm, R. C., andD. B. Ludlum, Coding properties of 7-methylguanine. Science153 (1966), 1403–1405.
Zachau, U. G., D. Dutting, andU. Feldmann, Nucleotide sequence of two serine-specific transfer ribonucleic acids. Angew. Chem. (Int. Ed.)5 (1966), 422–423.
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Viale, G.L. Biochemical patterns in brain tumours. Acta neurochir 21, 123–137 (1969). https://doi.org/10.1007/BF01540920
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DOI: https://doi.org/10.1007/BF01540920