DNA-DAMAGE INDUCED BY THE ENVIRONMENTAL CARCINOGEN BUTADIENE - IDENTIFICATION OF A DIEPOXYBUTANE-ADENINE ADDUCT AND ITS DETECTION BY P-32 POSTLABELING

To date only a few studies have been undertaken on DNA adducts formed by epoxybutene (EB) and diepoxybutane (DEB), the two active metabolite s of 1,3-butadiene. Our interests have focused on further investigatin g DNA alkylation by the two epoxides, especially in relation to the de velopment of a method for human biomonitoring. Here, following the rea ction of deoxyadenosine monophosphate and poly(dA-dT)(dA-dT) with DEB and subsequent HPLC, we have identified an adenine adduct. MS analyses indicate the structure of an adenine adducted by DEB at the N-6 posit ion. A HPLC/P-32-postlabelling method was developed for its measuremen t in DNA samples and the adduct was detected in calf thymus DNA and DN A from Chinese hamster ovary cells exposed to DEB. The 100% labelling efficiency during postlabelling, the amount of the adduct and its elut ion before the normal nucleotides during HPLC suggest it could be a su itable indicator of BUT exposure.