8-Arylguanine adducts from arenediazonium ions and DNA

Peter M. Gannett, Terence Lawson, M. Miller, D. D. Thakkar, J. W. Lord, W. M. Yau, B. Toth

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Arenediazonium ions (ArN2+) are genotoxic though the source of their genotoxicity is unknown. The present studies were undertaken to determine if reductive decomposition of ArN2+ to aryl radicals (Ar .) in the presence of calf thymus DNA (ctDNA) or in cells results in the formation of DNA adducts. We found that when arenediazonium ions of the general structure p-X-ArN2+ (X = CH3, CH2OCH3, CH2OH) are allowed to react with ctDNA or incubated with cells under conditions that produce p-X-Ar ., DNA adducts are formed with guanine. The structure of the adduct is the C8-substitution product derived from guanine and p-X-Ar .. Formation of p-X-Ar . was determined by ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The extent of C8-arylguanine adduction was measured by high performance liquid chromatography (HPLC) analysis of the DNA hydrosylate and comparison with authentic synthetic standards. The C8-arylguanine adducts observed to form may be important in regard to the genotoxicity of ArN2+, though other DNA adducts such as the N6-triazene of adenine or C8-aryladenine adducts can form. Finally, though the formation of C8-arylguanine adducts from arenediazonium ions has been proposed, this is the first report demonstrating their formation in DNA.

Original languageEnglish (US)
Pages (from-to)149-164
Number of pages16
JournalChemico-Biological Interactions
Volume101
Issue number2
DOIs
StatePublished - Aug 14 1996

Fingerprint

DNA Adducts
Guanine
Ions
DNA
Triazenes
Spin Trapping
High performance liquid chromatography
Adenine
Paramagnetic resonance
Substitution reactions
High Pressure Liquid Chromatography
Decomposition
calf thymus DNA

Keywords

  • C-arylguanine adducts
  • DMPO spin adduct
  • ESR
  • arenediazonium ion
  • aryl radicals

ASJC Scopus subject areas

  • Toxicology

Cite this

Gannett, P. M., Lawson, T., Miller, M., Thakkar, D. D., Lord, J. W., Yau, W. M., & Toth, B. (1996). 8-Arylguanine adducts from arenediazonium ions and DNA. Chemico-Biological Interactions, 101(2), 149-164. https://doi.org/10.1016/0009-2797(96)03722-2

8-Arylguanine adducts from arenediazonium ions and DNA. / Gannett, Peter M.; Lawson, Terence; Miller, M.; Thakkar, D. D.; Lord, J. W.; Yau, W. M.; Toth, B.

In: Chemico-Biological Interactions, Vol. 101, No. 2, 14.08.1996, p. 149-164.

Research output: Contribution to journalArticle

Gannett, PM, Lawson, T, Miller, M, Thakkar, DD, Lord, JW, Yau, WM & Toth, B 1996, '8-Arylguanine adducts from arenediazonium ions and DNA', Chemico-Biological Interactions, vol. 101, no. 2, pp. 149-164. https://doi.org/10.1016/0009-2797(96)03722-2
Gannett PM, Lawson T, Miller M, Thakkar DD, Lord JW, Yau WM et al. 8-Arylguanine adducts from arenediazonium ions and DNA. Chemico-Biological Interactions. 1996 Aug 14;101(2):149-164. https://doi.org/10.1016/0009-2797(96)03722-2
Gannett, Peter M. ; Lawson, Terence ; Miller, M. ; Thakkar, D. D. ; Lord, J. W. ; Yau, W. M. ; Toth, B. / 8-Arylguanine adducts from arenediazonium ions and DNA. In: Chemico-Biological Interactions. 1996 ; Vol. 101, No. 2. pp. 149-164.
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