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Development of a Mass Spectrometric Assay for 5,6,7,9-Tetrahydro-7-Hydroxy-9-Oximidazo [1,2-a]Purine in DNA Modified by 2-Chloro-Oxirane

  • Michael Müller
  • Frank Belas
  • Hitoshi Ueno
  • F. Peter Guengerich
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)

Abstract

Vinyl chloride is recognized as a human carcinogen. 2-Chlorooxirane, its biological reactive intermediate formed by the P450 enzyme system in the liver, and the rearrangement product chloroacetaldehyde give rise to the etheno (ε) DNA adducts. This type of modified DNA bases appears to be the molecular basis for the genotoxic effects of the parent compound, and site specific mutagenesis studies (Basu et al., 1993) show its mutagenicity. There is evidence that ε adducts might not only be formed by vinyl chloride metabolites but also be present at a certain level due to endogeneous sources (Misra et al., 1994).

Keywords

Vinyl Chloride Selective Reaction Monitoring Heavy Isotope Mass Spectrometric Assay Negative Electrospray Ionization Mass 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Basu. A.K., Wood, M.L., Niedernhofer, L.J., Ramos, L.A., and Essigmann, J.M. (1993) Mutagenic and gcnotoxic effects of three vinyl chloride-induced DNA lesions: 1,N 6-ethenoadenine, 3N 4-ethenocytosine and 4-amino-5-(imidazol-2-yl)imidazole Biochemistry 32, 12793–12801.PubMedCrossRefGoogle Scholar
  2. Cain, C.K., Mallette, M.F., and Taylor, E.C., Jr. (1946) Pyrimido[4,5-b]pyrazines. I. Synthesis of 6,7-symmetrically Substituted Derivatives. J. Am. Chem. Soc. 68, 1996–1999.PubMedCrossRefGoogle Scholar
  3. Fenn, J.B., Mann, M., Meng, C.K., and Wong, S.F. (1990) Electrospray ionization — principles and practice Mass Spec. Rev. 9, 37–70.CrossRefGoogle Scholar
  4. Gmeiner, H.W., and Poulter, CD. (1988) An efficient synthesis of [8-13C] adenine J. Org. Chem. 53, 1322–1323.CrossRefGoogle Scholar
  5. Guengerich, F.P., Persmark, M., and Humphreys, W.G. (1993) Formation of 1,N 2-and N 2,3-ethenoguanine from 2-halooxiranes: Isotopic labeling studies and isolation of a hemiaminal derivative of N 2-(2-oxoethyl)guanine Chem. Res. Toxicol 6, 635–648.PubMedCrossRefGoogle Scholar
  6. Lazarus, R.A., Sulewski, M.A., and Benkovic, S.J. (1982) Synthesis of [4a-13C]-6-methyltetrahydropterin J. Label. Compds. Radiopharm. 19, 1189–1195.CrossRefGoogle Scholar
  7. Little, D.P., Chorush, R.A., Speir, J.P., Senko, M.W., Kelleher, N.L., and McLafferty, F.W. (1994) Rapid sequencing of oligonucleotides by high-resolution mass spectrometry J. Am. Chem. Soc. 116, 4893–4897.CrossRefGoogle Scholar
  8. Misra, R.R., Chiang, S.-Y., and Swenberg, J.A. (1994) A comparison of two ultrasensitive methods for measuring l,N 6-etheno-2’-deoxyadenosine and 3,N 4-etheno-2’-deoxycytidine in cellular DNA Car0inogenesis 15, 1647–1652.CrossRefGoogle Scholar
  9. Potier, N., van Dorsselaer, A., Cordier, Y., Roch, O., and Bischoff, R. (1994) Negative electrospray ionization mass spectrometry of synthetic and chemically modified oligonucleotides Nucleic Acids Res. 22, 3895–3903.PubMedCrossRefGoogle Scholar
  10. Reddy, D.M., Rieger, R.A., Torres, M.C., and Iden, C.R. (1994) Analysis of synthetic oligodeoxynucleotides containing modified components by electrospray ionization mass spectrometry Analyt. Biochemistry 220, 200–207.CrossRefGoogle Scholar
  11. Sharma, M., Alderfer, J.L., and Box, H.C. (1983) Synthesis of morpholinium [13C] formate and its application in the synthesis of [8-13C] purine base J. Label. Compds. Radiopharm. 20, 1219–1225.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Michael Müller
    • 1
  • Frank Belas
    • 2
  • Hitoshi Ueno
    • 1
  • F. Peter Guengerich
    • 1
  1. 1.Department of Biochemistry and Center in Molecular ToxicologyVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of PharmacologyVanderbilt University School of MedicineNashvilleUSA

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