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. 1972 Jun;128(1):59–68. doi: 10.1042/bj1280059

Studies of the ethylation of rat liver transfer ribonucleic acid after administration of l-ethionine

A E Pegg 1
PMCID: PMC1173570  PMID: 5085644

Abstract

1. The ethylated nucleosides present in tRNA isolated from the livers of rats treated with 0.5g of l-ethionine/kg body wt. were investigated. Evidence that this tRNA contained N2-ethylguanine, N2N2-diethylguanine, N2-ethyl-N2-methylguanine, 7-ethylguanine, two ethylated pyrimidines and ethylated ribose groups was obtained. 2. Ethylation of bacterial tRNA was catalysed by extracts containing tRNA methylases prepared from rat liver by using S-adenosyl-l-ethionine as an ethyl donor, but the rate of ethylation was 20 times less than the rate of methylation with S-adenosyl-l-methionine as a methyl donor. 3. The principal product of such ethylation in vitro was N2-ethylguanine and traces of the other ethylated guanines and pyrimidines found in tRNA isolated from rats treated with ethionine in vivo were also found. 1-Ethyladenine was not formed, although 1-methyl-adenine is a major product of methylation of bacterial tRNA by these extracts, and 1-ethyladenine was not present in the rat liver tRNA isolated from ethionine-treated animals. 4. After injection of actinomycin D (15mg/kg body wt.) or l-methionine (1.0g/kg body wt.) before the ethionine, ethylation of tRNA was diminished by about 80% but not completely abolished. Administration of 1-aminocyclopentanecarboxylic acid (2.5g/kg body wt.) to inhibit the formation of S-adenosyl-l-ethionine inhibited ethylation of tRNA by 44%. 5. These results suggest that not all of the ethylation of tRNA that occurs in the livers of rats treated with ethionine is mediated by the action of tRNA methylases acting with S-adenosyl-l-ethionine as a substrate, but that this pathway does occur and accounts for a major part of the observed ethylation. 6. The results are discussed with reference to ethionine-induced hepatocarcinogenesis.

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Selected References

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  1. BROOM A. D., TOWNSEND L. B., JONES J. W., ROBINS R. K. PURINE NUCLEOSIDES. VI. FURTHER METHYLATION STUDIES OF NATURALLY OCCURRING PURINE NUCLEOSIDES. Biochemistry. 1964 Apr;3:494–500. doi: 10.1021/bi00892a005. [DOI] [PubMed] [Google Scholar]
  2. Baguley B. C., Staehelin M. Substrate specificity of adenine-specific transfer RNA methylase in normal and leukemic tissues. Eur J Biochem. 1968 Oct 17;6(1):1–7. doi: 10.1111/j.1432-1033.1968.tb00411.x. [DOI] [PubMed] [Google Scholar]
  3. Baguley B. C., Wehrli W., Staehelin M. In vitro methylation of yeast serine transfer ribonucleic acid. Biochemistry. 1970 Mar 31;9(7):1645–1649. doi: 10.1021/bi00809a026. [DOI] [PubMed] [Google Scholar]
  4. Baldessarini R. J., Kopin I. J. S-adenosylmethionine in brain and other tissues. J Neurochem. 1966 Aug;13(8):769–777. doi: 10.1111/j.1471-4159.1966.tb09884.x. [DOI] [PubMed] [Google Scholar]
  5. Baskin F., Dekker C. A. A rapid and specific assay for sugar methylation in ribonucleic acid. J Biol Chem. 1967 Nov 25;242(22):5447–5449. [PubMed] [Google Scholar]
  6. Brookes P. Quantitative aspects of the reaction of some carcinogens with nucleic acids and the possible significance of such reactions in the process of carcinogenesis. Cancer Res. 1966 Sep;26(9):1994–2003. [PubMed] [Google Scholar]
  7. Colburn N. H., Boutwell R. K. The binding of beta-propiolactone and some related alkylating agents to DNA, RNA, and protein of mouse skin; relation between tumor-initiating power of alkylating agents and their binding to DNA. Cancer Res. 1968 Apr;28(4):653–660. [PubMed] [Google Scholar]
  8. Craddock V. M. Methylation of transfer RNA and of ribosomal RNA in rat liver in the intact animal and the effect of carcinogens. Biochim Biophys Acta. 1969 Dec 16;195(2):351–369. doi: 10.1016/0005-2787(69)90642-x. [DOI] [PubMed] [Google Scholar]
  9. Craddock V. M., Villa-Trevino S., Magee P. N. Occurrence of 7-methylguanine in nucleic acids of rat liver. Biochem J. 1968 Mar;107(2):179–184. doi: 10.1042/bj1070179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DUNN D. B. Additional components in ribonucleic acid of rat-liver fractions. Biochim Biophys Acta. 1959 Jul;34:286–288. doi: 10.1016/0006-3002(59)90274-4. [DOI] [PubMed] [Google Scholar]
  11. Druckrey H., Preussmann R., Ivankovic S., Schmähl D. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z Krebsforsch. 1967;69(2):103–201. [PubMed] [Google Scholar]
  12. FARBER E. ETHIONINE CARCINOGENESIS. Adv Cancer Res. 1963;7:383–474. doi: 10.1016/s0065-230x(08)60986-0. [DOI] [PubMed] [Google Scholar]
  13. FARBER E., SHULL K. H., VILLA-TREVINO S., LOMBARDI B., THOMAS M. BIOCHEMICAL PATHOLOGY OF ACUTE HEPATIC ADENOSINETRIPHOSPHATE DEFICIENCY. Nature. 1964 Jul 4;203:34–40. doi: 10.1038/203034a0. [DOI] [PubMed] [Google Scholar]
  14. Farber E. Ethionine fatty liver. Adv Lipid Res. 1967;5:119–183. [PubMed] [Google Scholar]
  15. Farber E., McConomy J., Franzen B., Marroquin F., Stewart G. A., Magee P. N. Interaction between ethionine and rat liver ribonucleic acid and protein in vivo. Cancer Res. 1967 Oct;27(10):1761–1772. [PubMed] [Google Scholar]
  16. Friedman M., Shull K. H., Farber E. Highly selective in vivo ethylation of rat liver nuclear protein by ethionine. Biochem Biophys Res Commun. 1969 Mar 31;34(6):857–864. doi: 10.1016/0006-291x(69)90259-9. [DOI] [PubMed] [Google Scholar]
  17. Hancock R. L. Soluble RNA ethylase activity of normal and neoplastic mouse tissues. Cancer Res. 1968 Jul;28(7):1223–1230. [PubMed] [Google Scholar]
  18. Iwanami Y., Brown G. M. Methylated bases of transfer ribonucleic acid from HeLa and L cells. Arch Biochem Biophys. 1968 Mar 20;124(1):472–482. doi: 10.1016/0003-9861(68)90355-x. [DOI] [PubMed] [Google Scholar]
  19. Kuchino Y., Nishimura S. Nucleotide sequence specificities of guanylate residue-specific tRNA methylases from rat liver. Biochem Biophys Res Commun. 1970 Jul 27;40(2):306–313. doi: 10.1016/0006-291x(70)91010-7. [DOI] [PubMed] [Google Scholar]
  20. Lawley P. D. Effects of some chemical mutagens and carcinogens on nucleic acids. Prog Nucleic Acid Res Mol Biol. 1966;5:89–131. doi: 10.1016/s0079-6603(08)60232-9. [DOI] [PubMed] [Google Scholar]
  21. Leboy P. S. Stimulation of soluble ribonucleic acid methylase activity by polyamines. Biochemistry. 1970 Mar 31;9(7):1577–1584. doi: 10.1021/bi00809a016. [DOI] [PubMed] [Google Scholar]
  22. Lombardini J. B., Coulter A. W., Talalay P. Analogues of methionine as substrates and inhibitors of the methionine adenosyltransferase reaction. Deductions concerning the conformation of methionine. Mol Pharmacol. 1970 Sep;6(5):481–499. [PubMed] [Google Scholar]
  23. Lombardini J. B., Talalay P. Formation, functions and regulatory importance of S-adenosyl-L-methionine. Adv Enzyme Regul. 1970;9:349–384. doi: 10.1016/s0065-2571(71)80054-7. [DOI] [PubMed] [Google Scholar]
  24. MERITS I. Actinomycin inhibition of RNA synthesis in rat liver. Biochem Biophys Res Commun. 1963 Feb 6;10:254–259. doi: 10.1016/0006-291x(63)90426-1. [DOI] [PubMed] [Google Scholar]
  25. Magee P. N., Barnes J. M. Carcinogenic nitroso compounds. Adv Cancer Res. 1967;10:163–246. doi: 10.1016/s0065-230x(08)60079-2. [DOI] [PubMed] [Google Scholar]
  26. Miller J. A. Carcinogenesis by chemicals: an overview--G. H. A. Clowes memorial lecture. Cancer Res. 1970 Mar;30(3):559–576. [PubMed] [Google Scholar]
  27. NATORI Y. Studies on ethionine. VI. Sex-dependent behavior of methionine and ethionine in rats. J Biol Chem. 1963 Jun;238:2075–2080. [PubMed] [Google Scholar]
  28. Ortwerth B. J., Novelli G. D. Studies on the incorporation of L-ethionine-ethyl-l-14C into the transfer RNA of rat liver. Cancer Res. 1969 Feb;29(2):380–390. [PubMed] [Google Scholar]
  29. Pegg A. E. Methylation of purified transfer RNA preparations by extracts derived from rat kidney and kidney tumours. Biochim Biophys Acta. 1972 Mar 24;262(3):283–289. doi: 10.1016/0005-2787(72)90265-1. [DOI] [PubMed] [Google Scholar]
  30. Pegg A. E. Studies on inhibitors of mammalian tRNA methylases. FEBS Lett. 1971 Jul 15;16(1):13–16. doi: 10.1016/0014-5793(71)80672-5. [DOI] [PubMed] [Google Scholar]
  31. Pegg A. E. The effects of diamines and polyamines on enzymic methylation of nucleic acid. Biochim Biophys Acta. 1971 Apr 8;232(4):630–642. doi: 10.1016/0005-2787(71)90755-6. [DOI] [PubMed] [Google Scholar]
  32. Pegg A. E., Williams-Ashman H. G. Enzymic synthesis of spermine in rat prostate. Arch Biochem Biophys. 1970 Mar;137(1):156–165. doi: 10.1016/0003-9861(70)90422-4. [DOI] [PubMed] [Google Scholar]
  33. Pegg A. E., Williams-Ashman H. G. On the role of S-adenosyl-L-methionine in the biosynthesis of spermidine by rat prostate. J Biol Chem. 1969 Feb 25;244(4):682–693. [PubMed] [Google Scholar]
  34. Rodeh R., Feldman M., Littauer U. Z. Properties of soluble ribonucleic acid methylases from rat liver. Biochemistry. 1967 Feb;6(2):451–460. doi: 10.1021/bi00854a013. [DOI] [PubMed] [Google Scholar]
  35. Rosen L. Ethylation in vivo of purines in rat-liver RNA by L-ethionine. Biochem Biophys Res Commun. 1968 Nov 25;33(4):546–550. doi: 10.1016/0006-291x(68)90329-x. [DOI] [PubMed] [Google Scholar]
  36. SCHLENK F., DEPALMA R. E. The formation of S-adenosylmethionine in yeast. J Biol Chem. 1957 Dec;229(2):1037–1050. [PubMed] [Google Scholar]
  37. SMITH J. D., DUNN D. B. The occurrence of methylated guanines in ribonucleic acids from several sources. Biochem J. 1959 Jun;72(2):294–301. doi: 10.1042/bj0720294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Salvatore F., Zappia V., Shapiro S. K. Quantitative analysis of S-adenosylhomocysteine in liver. Biochim Biophys Acta. 1968 Jun 24;158(3):461–464. doi: 10.1016/0304-4165(68)90301-2. [DOI] [PubMed] [Google Scholar]
  39. Shank R. C., Magee P. N. Similarities between the biochemical actions of cycasin and dimethylnitrosamine. Biochem J. 1967 Nov;105(2):521–527. doi: 10.1042/bj1050521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shull K. H., McConomy J., Vogt M., Castillo A., Farber E. On the mechanism of induction of hepatic adenosine triphosphate deficiency by ethionine. J Biol Chem. 1966 Nov 10;241(21):5060–5070. [PubMed] [Google Scholar]
  41. Smith R. C., Salmon W. D. Formation of S-adenosylethionine by ethionine-treated rats. Arch Biochem Biophys. 1965 Jul;111(1):191–196. doi: 10.1016/0003-9861(65)90339-5. [DOI] [PubMed] [Google Scholar]
  42. Starr J. L., Sells B. H. Methylated ribonucleic acids. Physiol Rev. 1969 Jul;49(3):623–669. doi: 10.1152/physrev.1969.49.3.623. [DOI] [PubMed] [Google Scholar]
  43. Swann P. F., Magee P. N. Nitrosamine-induced carcinogenesis. The alklylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem J. 1968 Nov;110(1):39–47. doi: 10.1042/bj1100039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Swann P. F., Magee P. N. Nitrosamine-induced carcinogenesis. The alkylation of N-7 of guanine of nucleic acids of the rat by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate. Biochem J. 1971 Dec;125(3):841–847. doi: 10.1042/bj1250841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Swann P. F., Pegg A. E., Hawks A., Farber E., Magee P. N. Evidence for ethylation of rat liver deoxyribonucleic acid after administration of ethionine. Biochem J. 1971 Jun;123(2):175–181. doi: 10.1042/bj1230175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. WYATT G. R. The nucleic acids of some insect viruses. J Gen Physiol. 1952 Nov;36(2):201–205. doi: 10.1085/jgp.36.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Weinstein I. B., Grunberger D., Fujimura S., Fink L. M. Chemical carcinogens and RNA. Cancer Res. 1971 May;31(5):651–655. [PubMed] [Google Scholar]

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