Styrene oxide-induced 2'-deoxycytidine adducts: implications for the mutagenicity of styrene oxide

Chem Biol Interact. 2000 Jun 1;126(3):201-13. doi: 10.1016/s0009-2797(00)00165-4.

Abstract

The reaction between 2'-deoxycytidine and styrene 7,8-oxide (SO) resulted in alkylation at the 3-position and at the O(2)-position through the alpha- and beta-carbons of the epoxide but at the N(4)-position only through the alpha-carbon. The 3-alkylated adducts were found to deaminate to the corresponding 2'-deoxyuridine adducts (37 degrees C, pH 7.4) with half-lives of 6 min and 2.4 h for the alpha- and beta-isomers, respectively. The N(4)-alkylated products were stable at neutral pH. The O(2)-alkylated products were unstable being prone to depyrimidation and to isomerisation between alpha- and beta-isomers. In SO-treated double-stranded DNA, enzymatic hydrolysis allowed the identification of the beta3-deoxyuridine and alphaN(4)-deoxycytidine adducts (1.9 and 0.5% of total alkylation, respectively), in addition to the previously identified DNA-adducts. The 3-substituted uracil may have implications for the mutagenicity of SO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • DNA Adducts / chemical synthesis*
  • DNA Damage*
  • Deamination
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / chemistry*
  • Deoxyuridine / analogs & derivatives
  • Deoxyuridine / chemistry
  • Epoxy Compounds / chemistry*
  • Mass Spectrometry
  • Mutagens / chemistry*
  • Salmon / genetics
  • Spectrophotometry, Ultraviolet

Substances

  • DNA Adducts
  • Epoxy Compounds
  • Mutagens
  • Deoxycytidine
  • styrene oxide
  • Deoxyuridine