CHARACTERIZATION OF S-[2-(N1-ADENYL)ETHYL]GLUTATHIONE AS AN ADDUCT FORMED IN RNA AND DNA FROM 1,2-DIBROMOETHANE

The major DNA adduct derived from 1,2-dibromoethane is known to be S-[2-(Af7-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 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 N'-ethyladenine in low yield. The Raney Ni reaction was accompanied by considerable formation of the corresponding N-adenine derivative via Dimroth rearrangement. Another adduct was identified as S-[2-(Ar7-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-(Arl-Adenyl)ethyl]glutathione was formed in rat liver RNA and DNA. Rates of loss of the minor adducts from rat liver DNA are very similar to the rate of loss of S-[2-(V7-guanyl)ethyl]glutathione (f1/2 ~ 100 h), and no evidence for unusual persistence was found. © 1990, American Chemical Society. All rights reserved.