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. 1997 May 15;25(10):1897–1902. doi: 10.1093/nar/25.10.1897

Glyoxal, a major product of DNA oxidation, induces mutations at G:C sites on a shuttle vector plasmid replicated in mammalian cells.

N Murata-Kamiya 1, H Kamiya 1, H Kaji 1, H Kasai 1
PMCID: PMC146688  PMID: 9115355

Abstract

Glyoxal is a major product of DNA oxidation in which Fenton-type oxygen free radical-forming systems are involved. To determine the mutation spectrum of glyoxal in mammalian cells and to compare the spectrum with those observed in other experimental systems, we analyzed mutations in a bacterial suppressor tRNA gene (supF) in the shuttle vector plasmid pMY189. We treated pMY189 with glyoxal and immediately transfected it into simian COS-7 cells. The cytotoxicity and mutation frequency increased according to the dose of glyoxal. The majority of glyoxal-induced mutations (48%) were single-base substitutions. Eighty three percent of the single-base substitutions occurred at G:C base pairs. Among them, G:C-->T:A transversions were predominant, followed by G:C-->C:G transversions and G:C-->A:T transitions. A:T-->T:A transversions were also observed. Mutational hotspots within the supF gene were detected. These results suggest that glyoxal may play an important role in mutagenesis induced by oxygen free radicals.

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Selected References

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  1. Akasaka S., Takimoto K., Yamamoto K. G:C-->T:A and G:C-->C:G transversions are the predominant spontaneous mutations in the Escherichia coli supF gene: an improved lacZ(am) E. coli host designed for assaying pZ189 supF mutational specificity. Mol Gen Genet. 1992 Nov;235(2-3):173–178. doi: 10.1007/BF00279358. [DOI] [PubMed] [Google Scholar]
  2. Akasaka S., Yamamoto K. Hydrogen peroxide induces G:C to T:A and G:C to C:G transversions in the supF gene of Escherichia coli. Mol Gen Genet. 1994 Jun 3;243(5):500–505. doi: 10.1007/BF00284197. [DOI] [PubMed] [Google Scholar]
  3. Akasaka S., Yamamoto K. Mutagenesis resulting from DNA damage by lipid peroxidation in the supF gene of Escherichia coli. Mutat Res. 1994 Sep;315(2):105–112. doi: 10.1016/0921-8777(94)90011-6. [DOI] [PubMed] [Google Scholar]
  4. Akasaka S., Yamamoto K. Mutational specificity of the ferrous ion in a supF gene of Escherichia coli. Biochem Biophys Res Commun. 1995 Aug 4;213(1):74–80. doi: 10.1006/bbrc.1995.2100. [DOI] [PubMed] [Google Scholar]
  5. Basu A. K., Loechler E. L., Leadon S. A., Essigmann J. M. Genetic effects of thymine glycol: site-specific mutagenesis and molecular modeling studies. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7677–7681. doi: 10.1073/pnas.86.20.7677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bjeldanes L. F., Chew H. Mutagenicity of 1,2-dicarbonyl compounds: maltol, kojic acid, diacetyl and related substances. Mutat Res. 1979 Aug;67(4):367–371. doi: 10.1016/0165-1218(79)90034-x. [DOI] [PubMed] [Google Scholar]
  7. Breen A. P., Murphy J. A. Reactions of oxyl radicals with DNA. Free Radic Biol Med. 1995 Jun;18(6):1033–1077. doi: 10.1016/0891-5849(94)00209-3. [DOI] [PubMed] [Google Scholar]
  8. Dorado L., Ruis Montoya M. R., Rodríguez Mellado J. M. A contribution to the study of the structure-mutagenicity relationship for alpha-dicarbonyl compounds using the Ames test. Mutat Res. 1992 Oct;269(2):301–306. doi: 10.1016/0027-5107(92)90212-k. [DOI] [PubMed] [Google Scholar]
  9. Feig D. I., Sowers L. C., Loeb L. A. Reverse chemical mutagenesis: identification of the mutagenic lesions resulting from reactive oxygen species-mediated damage to DNA. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6609–6613. doi: 10.1073/pnas.91.14.6609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gentil A., Renault G., Madzak C., Margot A., Cabral-Neto J. B., Vasseur J. J., Rayner B., Imbach J. L., Sarasin A. Mutagenic properties of a unique abasic site in mammalian cells. Biochem Biophys Res Commun. 1990 Dec 14;173(2):704–710. doi: 10.1016/s0006-291x(05)80092-0. [DOI] [PubMed] [Google Scholar]
  11. Harman D. The aging process. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7124–7128. doi: 10.1073/pnas.78.11.7124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hauser J., Seidman M. M., Sidur K., Dixon K. Sequence specificity of point mutations induced during passage of a UV-irradiated shuttle vector plasmid in monkey cells. Mol Cell Biol. 1986 Jan;6(1):277–285. doi: 10.1128/mcb.6.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ishizaki K., Nishizawa K., Mimaki S., Aizawa S. UV-induced mutations of supF gene on a shuttle vector plasmid in p53-deficient mouse cells are qualitatively different from those in wild-type cells. Mutat Res. 1996 Sep 2;364(1):43–49. doi: 10.1016/0921-8777(96)00020-1. [DOI] [PubMed] [Google Scholar]
  14. Kamiya H., Kasai H. Substitution and deletion mutations induced by 2-hydroxyadenine in Escherichia coli: effects of sequence contexts in leading and lagging strands. Nucleic Acids Res. 1997 Jan 15;25(2):304–311. doi: 10.1093/nar/25.2.304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kamiya H., Murata-Kamiya N., Koizume S., Inoue H., Nishimura S., Ohtsuka E. 8-Hydroxyguanine (7,8-dihydro-8-oxoguanine) in hot spots of the c-Ha-ras gene: effects of sequence contexts on mutation spectra. Carcinogenesis. 1995 Apr;16(4):883–889. doi: 10.1093/carcin/16.4.883. [DOI] [PubMed] [Google Scholar]
  16. Kamiya H., Suzuki M., Komatsu Y., Miura H., Kikuchi K., Sakaguchi T., Murata N., Masutani C., Hanaoka F., Ohtsuka E. An abasic site analogue activates a c-Ha-ras gene by a point mutation at modified and adjacent positions. Nucleic Acids Res. 1992 Sep 11;20(17):4409–4415. doi: 10.1093/nar/20.17.4409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kasai H., Hayami H., Yamaizumi Z., SaitôH, Nishimura S. Detection and identification of mutagens and carcinogens as their adducts with guanosine derivatives. Nucleic Acids Res. 1984 Feb 24;12(4):2127–2136. doi: 10.1093/nar/12.4.2127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kasai H., Kumeno K., Yamaizumi Z., Nishimura S., Nagao M., Fujita Y., Sugimura T., Nukaya H., Kosuge T. Mutagenicity of methylglyoxal in coffee. Gan. 1982 Oct;73(5):681–683. [PubMed] [Google Scholar]
  19. Kouchakdjian M., Marinelli E., Gao X. L., Johnson F., Grollman A., Patel D. NMR studies of exocyclic 1,N2-propanodeoxyguanosine adducts (X) opposite purines in DNA duplexes: protonated X(syn).A(anti) pairing (acidic pH) and X(syn).G(anti) pairing (neutral pH) at the lesion site. Biochemistry. 1989 Jun 27;28(13):5647–5657. doi: 10.1021/bi00439a047. [DOI] [PubMed] [Google Scholar]
  20. Kraemer K. H., Seidman M. M. Use of supF, an Escherichia coli tyrosine suppressor tRNA gene, as a mutagenic target in shuttle-vector plasmids. Mutat Res. 1989 Mar-May;220(2-3):61–72. doi: 10.1016/0165-1110(89)90011-0. [DOI] [PubMed] [Google Scholar]
  21. Loeb L. A., James E. A., Waltersdorph A. M., Klebanoff S. J. Mutagenesis by the autoxidation of iron with isolated DNA. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3918–3922. doi: 10.1073/pnas.85.11.3918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matsuda T., Yagi T., Kawanishi M., Matsui S., Takebe H. Molecular analysis of mutations induced by 2-chloroacetaldehyde, the ultimate carcinogenic form of vinyl chloride, in human cells using shuttle vectors. Carcinogenesis. 1995 Oct;16(10):2389–2394. doi: 10.1093/carcin/16.10.2389. [DOI] [PubMed] [Google Scholar]
  23. McBride T. J., Preston B. D., Loeb L. A. Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry. 1991 Jan 8;30(1):207–213. doi: 10.1021/bi00215a030. [DOI] [PubMed] [Google Scholar]
  24. McBride T. J., Schneider J. E., Floyd R. A., Loeb L. A. Mutations induced by methylene blue plus light in single-stranded M13mp2. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6866–6870. doi: 10.1073/pnas.89.15.6866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Moraes E. C., Keyse S. M., Tyrrell R. M. Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis. Carcinogenesis. 1990 Feb;11(2):283–293. doi: 10.1093/carcin/11.2.283. [DOI] [PubMed] [Google Scholar]
  26. Moriya M. Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G.C-->T.A transversions in simian kidney cells. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1122–1126. doi: 10.1073/pnas.90.3.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Moriya M., Zhang W., Johnson F., Grollman A. P. Mutagenic potency of exocyclic DNA adducts: marked differences between Escherichia coli and simian kidney cells. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11899–11903. doi: 10.1073/pnas.91.25.11899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murata-Kamiya N., Kamiya H., Iwamoto N., Kasai H. Formation of a mutagen, glyoxal, from DNA treated with oxygen free radicals. Carcinogenesis. 1995 Sep;16(9):2251–2253. doi: 10.1093/carcin/16.9.2251. [DOI] [PubMed] [Google Scholar]
  29. Nishiyama T., Hagiwara Y., Hagiwara H., Shibamoto T. Inhibitory effect of 2"-O-glycosyl isovitexin and alpha-tocopherol on genotoxic glyoxal formation in a lipid peroxidation system. Food Chem Toxicol. 1994 Nov;32(11):1047–1051. doi: 10.1016/0278-6915(94)90145-7. [DOI] [PubMed] [Google Scholar]
  30. Rich A., RajBhandary U. L. Transfer RNA: molecular structure, sequence, and properties. Annu Rev Biochem. 1976;45:805–860. doi: 10.1146/annurev.bi.45.070176.004105. [DOI] [PubMed] [Google Scholar]
  31. Sayato Y., Nakamuro K., Ueno H. Mutagenicity of products formed by ozonation of naphthoresorcinol in aqueous solutions. Mutat Res. 1987 Nov;189(3):217–222. doi: 10.1016/0165-1218(87)90055-3. [DOI] [PubMed] [Google Scholar]
  32. Schaaper R. M., Kunkel T. A., Loeb L. A. Infidelity of DNA synthesis associated with bypass of apurinic sites. Proc Natl Acad Sci U S A. 1983 Jan;80(2):487–491. doi: 10.1073/pnas.80.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Seidman M. M., Dixon K., Razzaque A., Zagursky R. J., Berman M. L. A shuttle vector plasmid for studying carcinogen-induced point mutations in mammalian cells. Gene. 1985;38(1-3):233–237. doi: 10.1016/0378-1119(85)90222-7. [DOI] [PubMed] [Google Scholar]
  34. Shapiro R., Hachmann J. The reaction of guanine derivatives with 1,2-dicarbonyl compounds. Biochemistry. 1966 Sep;5(9):2799–2807. doi: 10.1021/bi00873a004. [DOI] [PubMed] [Google Scholar]
  35. Stary A., Sarasin A. Simian virus 40 (SV40) large T antigen-dependent amplification of an Epstein-Barr virus-SV40 hybrid shuttle vector integrated into the human HeLa cell genome. J Gen Virol. 1992 Jul;73(Pt 7):1679–1685. doi: 10.1099/0022-1317-73-7-1679. [DOI] [PubMed] [Google Scholar]
  36. Tudek B., Laval J., Boiteux S. SOS-independent mutagenesis in lacZ induced by methylene blue plus visible light. Mol Gen Genet. 1993 Jan;236(2-3):433–439. doi: 10.1007/BF00277144. [DOI] [PubMed] [Google Scholar]

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