Butadiene monoxide and deoxyguanosine alkylation products at the N7-position.
3,4-Epoxy-1-butene, an active metabolite of 1,3-butadiene, was reacted with guanosine, deoxyguanosine and calf thymus DNA. The products were isolated and positively identified using various spectroscopic techniques. Treatment of calf thymus-DNA with 3,4-epoxy-1-butene yielded two N7-guanine adducts of equal stability. Depurination by neutral hydrolysis showed that 7-(2-hydroxy-3-buten-1-yl)guanine (compound I) was formed in greater quantities compared to its regioisomer 7-(1-hydroxy-3-buten-2-yl)guanine (compound II); spontaneous depurination experiments showed that compound I was released in the highest proportion. The circular dichroism spectral studies with R and S 3,4-epoxy-1-butene revealed that the reaction mechanism at aqueous neutral pH media is more similar to SN2-type rather than SN1-type. The HPLC-electrochemical detection method used to carry out the DNA alkylation study provides a rapid and sensitive quantitation of N7 guanine adducts in biological fluids. This serves as a useful tool for further human biomonitoring experiments.
Neagu
I
I
Institute of Occupational Health, Molecular Dosimetry Group, Helsinki, Finland.
Koivisto
P
P
Neagu
C
C
Kostiainen
R
R
Stenby
K
K
Peltonen
K
K
D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism*
D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; D003849:Deoxyguanosine