Consequences of 1,3-butadiene DNA adducts – R,R-N6,N6-DHB-dA and R,S-1,N6-g-HMHP-dA – on DNA base pairing

Abstract

DNA is the hereditary material in humans and almost all other organisms. Unfortunately, upon exposure to carcinogenic species and other compounds, our DNA can be damaged in a variety of ways. An example of DNA damage includes the formation of bulky nucleobase addition products (adducts), which may give rise to cancer. This poster focuses on adducts formed upon exposure to 1,3-butadiene – a human carcinogen that has been associated with an increased incidence of leukemia (cancer of the blood cells). Sources of 1,3-butadiene exposure include automobile exhaust and tobacco smoke, as well as polluted water and air at or near chemical, plastic or rubber facilities. In order to understand the consequences of DNA exposure to 1,2,3,4-diepoxybutane – a metabolite of 1,3-butadiene –  this study examines the hydrogen-bonding properties of two adenine (dA) adducts formed upon addition of a bulky moiety to the N6 position, namely the R,R-N6,N6-DHB-dA and R,S-1,N6- g-HMHP-dA adducts. Previous studies have shown that human translesion DNA polymerases hand k preferentially incorporated A, C, G or T opposite R,R-N6,N6-DHB-dA, and A, G or T opposite R,S-1,N6-g-HMHP-dA. This study seeks to explain the observed mutagenicity of these adducts and is the first step in determining the effect of these adducts on the DNA duplex.

Figure 1. 1,3-butadiene adducts R,R-N6,N6-DHB-dA (left) and R,S-1,N6-g-HMHP-dA (right)