title: Formation of S-[2-(N7-guanyl)ethyl] adducts by the postulated S-(2-chloroethyl)cysteinyl and S-(2-chloroethyl)glutathionyl conjugates of 1,2-dichloroethane.
abstract: The formation of S-[2-(N7-guanyl)ethyl]glutathione (GEG) from dihaloethanes is postulated to occur through two intermediates: the S-(2-haloethyl)glutathione conjugate and the corresponding episulfonium ion. We report the formation of GEG when deoxyguanosine (dG) was incubated with chemically synthesized S-(2-chloroethyl)glutathione (CEG). The depurination of GEG was shown to be first order with a half-life of 7.4 +/- 0.4 h at 27 degrees C. Evidence is also presented for the formation of S-[2-(N7-guanyl)ethyl]-L-cysteine (GEC) in incubation mixtures containing dG and S-(2-chloroethyl)-L-cysteine (CEC), the corresponding cysteine conjugate of CEG. This finding demonstrates that this (haloethyl)cysteine conjugate does not require activation by enzymatic action of cysteine conjugate beta-lyase but, instead, can directly alkylate DNA. The half-life of the depurination of GEC was 6.5 +/- 0.9 h, which is no different from that of GEG. Of the two conjugates, CEC is a somewhat more active alkylating agent toward dG than CEG as N7-guanylic adduct was detected in reaction mixtures with lower concentrations of CEC than with CEG.
mesh_terms: D055598:Chemical Phenomena; D002621:Chemistry; D003545:Cysteine / Q000031:analogs & derivatives*; D018736:DNA Adducts; D003849:Deoxyguanosine; D004000:Dichloroethylenes; D005978:Glutathione / Q000031:analogs & derivatives*; D006843:Hydrocarbons, Chlorinated; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D018736:DNA Adducts; D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; C045285:S-(2-chloroethyl)cysteine; C038886:S-(2-(N(7)-guanyl)ethyl)glutathione; D003849:Deoxyguanosine; D005978:Glutathione; D003545:Cysteine; C046570:S-(2-chloroethyl)glutathione