Styrene oxide-induced 2'-deoxycytidine adducts: implications for the mutagenicity of styrene oxide.
The reaction between 2'-deoxycytidine and styrene 7,8-oxide (SO) resulted in alkylation at the 3-position and at the O(2)-position through the alpha- and beta-carbons of the epoxide but at the N(4)-position only through the alpha-carbon. The 3-alkylated adducts were found to deaminate to the corresponding 2'-deoxyuridine adducts (37 degrees C, pH 7.4) with half-lives of 6 min and 2.4 h for the alpha- and beta-isomers, respectively. The N(4)-alkylated products were stable at neutral pH. The O(2)-alkylated products were unstable being prone to depyrimidation and to isomerisation between alpha- and beta-isomers. In SO-treated double-stranded DNA, enzymatic hydrolysis allowed the identification of the beta3-deoxyuridine and alphaN(4)-deoxycytidine adducts (1.9 and 0.5% of total alkylation, respectively), in addition to the previously identified DNA-adducts. The 3-substituted uracil may have implications for the mutagenicity of SO.
Koskinen
M
M
Center for Nutrition and Toxicology, Department of Biosciences at Novum, Karolinska Institute, S-141 57, Huddinge, Sweden. mikko.koskinen@cnt.ki.se
Calebiro
D
D
Hemminki
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000138:chemical synthesis*; D004249:DNA Damage; D003641:Deamination; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry*; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D013058:Mass Spectrometry; D009153:Mutagens / Q000737:chemistry*; D012474:Salmon / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet
D018736:DNA Adducts; D004852:Epoxy Compounds; D009153:Mutagens; D003841:Deoxycytidine; C013690:styrene oxide; D003857:Deoxyuridine