Identification and characterization of deoxyguanosine adducts of mutagenic beta-alkyl-substituted acrolein congeners.
The reaction of the mutagenic beta-alkyl-substituted acroleins (E)-2-pentenal, (E)-2-hexenal, (E,E)-2,4-hexadienal, and 3,3-dimethylacrolein with nucleosides and 5'-mononucleotides was studied. We found two different types of adducts with deoxyguanosine and 2'-deoxyguanosine 5'-monophosphate. No adducts could be isolated with either nucleosides other than deoxyguanosine or nucleotides other than 2'-deoxyguanosine 5'-monophosphate. With pentenal, hexenal, and 3,3-dimethylacrolein, we identified and characterized 1,N2-cyclic adducts and 7,8-cyclic adducts. The 1,N2-adducts of pentenal and hexenal were mixtures of diastereomers, one pair in which the substituents in the newly formed ring were trans (6S,8S and 6R,8R) and another in which they were cis. The cis isomers were formed to a much lesser extent. In all cases, the regioisomer is formed in which the OH group is vicinal to the N-1 atom of the guanine moiety. In the case of the 7,8 adducts, the ribose cleaved spontaneously during the reaction, and a mixture of isomers in which the substituents were cis and trans in the newly formed tetrahydropyrrole ring was observed. Since these compounds form adducts in a similar way to crotonaldehyde and are also mutagenic like crotonaldehyde, it was proposed to regard them as carcinogenic, like crotonaldehyde, unless experimental examination demonstrates nonmutagenicity.
Eder
E
E
Institute of Toxicology, University of Würzburg, FRG.
Hoffman
C
C
D000171:Acrolein / Q000031:analogs & derivatives / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003848:Deoxyguanine Nucleotides / Q000032:analysis; D003849:Deoxyguanosine / Q000032:analysis*; D004563:Electrochemistry; D006147:Guanine / Q000737:chemistry; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009153:Mutagens / Q000032:analysis*; D009705:Nucleosides / Q000138:chemical synthesis; D009711:Nucleotides / Q000138:chemical synthesis; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D003848:Deoxyguanine Nucleotides; D009153:Mutagens; D009705:Nucleosides; D009711:Nucleotides; C077233:2'-deoxyguanylic acid; D006147:Guanine; D000171:Acrolein; D003849:Deoxyguanosine