title: Reaction of trans-4-N-acetoxy-N-acetylaminostilbene with guanosine, deoxyguanosine, RNA and DNA in vitro: predominant product is a cyclic N2,N3-guanine adduct.
abstract: The model ultimate carcinogen trans-4-N-acetoxy-N-acetylaminostilbene was reacted with guanosine, deoxyguanosine, RNA and DNA using differently labeled reactants. The nucleoside as well as the deoxynucleoside yielded predominantly four cyclic guanine adducts: (S,S)- and (R,R)-guanine-N2,beta-N3,alpha-N-acetyl-aminobibenzyl and the regioisomers with the N2,alpha-N3,beta-attachment in a ratio of 9:9:1:1. The same adducts predominate in RNA and DNA which demonstrates that guanine reacts most avidly among the bases. The stability of the N-glycosidic bond is quite different between ribosides and deoxyribosides. Under neutral conditions, the riboside derivatives are stable, whereas deoxyribose is cleaved off rather readily. As a consequence DNA depurinizes to some extent during the in vitro reaction and during enzymatic digestion. On the other hand, N2,N3-attachment of the acetylaminostilbene moiety to guanine appears to impair the activity of nucleases for steric reasons. This could explain the incomplete enzymatic hydrolysis of modified nucleic acids. The results provide an important basis for further investigations to identify the nucleic acid adducts generated in vivo.
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA; D003849:Deoxyguanosine; D006147:Guanine / Q000031:analogs & derivatives*; D006151:Guanosine; D066298:In Vitro Techniques; D012313:RNA; D012441:Saccharomyces cerevisiae; D013056:Spectrophotometry, Ultraviolet; D013267:Stilbenes
chemical_list: D013267:Stilbenes; D006151:Guanosine; C006363:N-acetoxy-4-acetylaminostilbene; D006147:Guanine; D012313:RNA; D004247:DNA; D003849:Deoxyguanosine