8-Arylguanine adducts from arenediazonium ions and DNA

Peter M. Gannett, Terence A 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 (ArN 2 + ) are genotoxic though the source of their genotoxicity is unknown. The present studies were undertaken to determine if reductive decomposition of ArN 2 + 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-ArN 2 + (X = CH 3 , CH 2 OCH 3 , CH 2 OH) 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 C 8 -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 C 8 -arylguanine adduction was measured by high performance liquid chromatography (HPLC) analysis of the DNA hydrosylate and comparison with authentic synthetic standards. The C 8 -arylguanine adducts observed to form may be important in regard to the genotoxicity of ArN 2 + , though other DNA adducts such as the N 6 -triazene of adenine or C 8 -aryladenine adducts can form. Finally, though the formation of C 8 -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. A., 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 A; 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, TA, 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 TA, 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 A ; 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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