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-bnten-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 S(N)2-type rather than S(N)1-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.