Characterization of S-[2-(N1-adenyl)ethyl]glutathione as an adduct formed in RNA and DNA from 1,2-dibromoethane

Chem Res Toxicol. 1990 Nov-Dec;3(6):587-94. doi: 10.1021/tx00018a015.

Abstract

The major DNA adduct derived from 1,2-dibromoethane is known to be S-[2-(N7-guanyl)-ethyl]glutathione; minor nucleic acid DNA adducts were characterized in view of the possibility that some might be unusually persistent or biologically active. RNA was modified in vitro by treatment with 1,2-dibromoethane and glutathione in the presence of rat liver cytosol, and bases were released by mild acid hydrolysis, which liberated greater than 99% of the bound radioactivity. One of the minor adducts was identified as S-[2-(N1-adenyl)ethyl]glutathione on the basis of its UV, mass, and NMR spectra. This adduct could be synthesized by reaction of S-(2-chloroethyl)-glutathione with adenosine. The material was desulfurized by treatment with Raney Ni to give N1-ethyladenine in low yield. The Raney Ni reaction was accompanied by considerable formation of the corresponding N6-adenine derivative via Dimroth rearrangement. Another adduct was identified as S-[2-(N7-guanyl)ethyl]cysteinylglycine by its UV, mass, and NMR spectra, but the material was demonstrated to be formed from the major DNA adduct, S-[2-(N7-guanyl)-ethyl]glutathione under conditions of mild acid hydrolysis. The imidazole ring opened derivative of S-[2-(N7-guanyl)ethyl]glutathione was synthesized and found not to be formed in DNA in vitro or in vivo. The two remaining minor adducts account for 1-2% of the total binding, but insufficient quantities were recovered to allow for structure determination; however, neither of these (uncharacterized) minor products are seen after the reaction of S-(2-chloroethyl)glutathione with guanosine or adenosine. S-[2-(N1-Adenyl)ethyl]glutathione was formed in rat liver RNA and DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA / metabolism*
  • Ethylene Dibromide / metabolism*
  • Glutathione / metabolism*
  • RNA / metabolism*
  • Rats

Substances

  • Ethylene Dibromide
  • RNA
  • DNA
  • Glutathione