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The alkylating reactions of 1,2-epoxy-3,4-butene (EB) and 1,2,3,4-diepoxybutane (DEB)-the important metabolites of rodent carcinogenic 1,3-butadiene, with adenine and cytosine andinteraction with fragment of DNA on major groove-have been computed. Results show thatthere are little differences in activation energy between EB and DEB, so it is difficult to explain the fact that the mutagenicity of DEB is greater (about 100-fold) than that of EB by the ability of alkylation. it is also known that DEB can interstrand cross-link with DNA through two times alkylating reactions, whereas EB cannot. So this may contribute to the significant different genotoxicity of the two agents. Meanwhile, DEB can interstrand cross-link with many sequences of DNA in major groove vs. two in minor groove, which increases opportunity of interstrand cross-link with DNA in major groove. This difference may be the reason of base selection of DEB mutation. The deformation of some cross-linked DNA may also contribute to this selectio
The alkylating reactions of 1,2-epoxy-3,4-butene (EB) and 1,2,3,4-diepoxybutane (DEB) -the important metabolites of rodent carcinogenic 1,3-butadiene, with adenine and cytosine andinteraction with fragment of DNA on major groove-have been computed. Results show that little differences in activation energy between EB and DEB, so it is difficult to explain the fact that the mutagenicity of DEB is greater (about 100-fold) than that of EB by the ability of alkylation. It is also known that DEB can interstrand cross-link with DNA through two times alkylating reactions, whereas EB can not. So, it may contribute to the significant different genotoxicity of the two agents. Meanwhile, DEB can interstrand cross- link with many sequences of DNA in major groove vs. two in minor groove, which offers opportunity of interstrand cross-link with DNA in major groove. This difference may be the reason of base selection of DEB mutation. The deformation of some cross-linked DNA may also contribut e to this selectio