Identification and characterization of deoxyguanosine-crotonaldehyde adducts. Formation of 7,8 cyclic adducts and 1,N2,7,8 bis-cyclic adducts.
Crotonaldehyde, a chemically reactive alpha,beta-unsaturated carbonyl compound, is an important industrial chemical and a ubiquitous environmental pollutant. It has been shown to be carcinogenic and mutagenic. We have studied the reaction of crotonaldehyde with nucleosides and 5'-mononucleotides and found three different types of adducts with deoxyguanosine and 2'-deoxyguanosine 5'-monophosphate. No adducts could be isolated either with nucleosides other than deoxyguanosine or with nucleotides other than 2'-deoxyguanosine 5'-monophosphate. With crotonaldehyde, deoxyguanosine produced 1,N2 and 7,8 adducts as well as 1,N2/7,8 bis-adducts. The 1,N2 adducts were mixtures of diastereomers: one pair in which the substituents in the newly formed ring were trans [adduct Ia (6S,8S) and (6R,8R)], about 94%, and another pair Ib in which they were cis. In the case of the 7,8-adducts IIa,b, the ribose was cleaved and a mixture of isomers in which the substituents were cis-IIa and trans-IIb (2:1) in the newly formed tetrahydropyrrole ring was observed. A 3:2 cis-IIIa and trans-IIIb mixture of 1,N2,7,8 bis-adducts was found with the isomerism in the newly formed tetrahydropyrrole ring in analogy to the 7,8 adducts IIa,b. The corresponding bis-adduct with the cis form in the newly formed tetrahydropyrimidine ring was not observed.
Eder
E
E
Institute of Toxicology, University of Würzburg, Germany.
Hoffman
C
C
D000447:Aldehydes / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003848:Deoxyguanine Nucleotides / Q000737:chemistry; D003849:Deoxyguanosine / Q000032:analysis / Q000737:chemistry*; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000447:Aldehydes; D003848:Deoxyguanine Nucleotides; C007257:2'-deoxyguanosine 5'-phosphate; C012796:2-butenal; D003849:Deoxyguanosine