The metabolic activation of dibenz[a,c]anthracene

In rat liver microsomal preparations, the 10, 11-dihydro-diolof dibenz[a, c]anthracene (DBA) is metabolized to r-10, t-11-dihydroxy-t-12,13-oxy-10, 11, 12, 13-tetrahydro-dibenz[a, c]anthracene (anti-DBA10, 11-diol 12, 13-oxide), the anti isomer of a non-bay-regiondiol-epoxide of DBA. When ³-labelled DBA or trans-10, 11-di-hydro-10,ll-dihydroxydibenz[a, c]anthracene were metabolized in thissystem in the presence of DNA or when ³H-labelled DBA was addedto primary cultures of hamster embryo cells, covalent reactionsof hydrocarbon metabolites with DNA occurred. The chromato-graphiccharacteristics of the radioactive hydrocarbon — deoxyribonucleosideadducts formed in these reactions were examined using SephadexLH20 column chromatography and high pressure liquid chromato-graphy.The results showed that whilst some of the radioactive hydrocarbon— deoxyribonucleoside adducts formed were indistinguishablefrom adducts that were formed when anti-DBA 10, 11-diol 12,13-oxide reacted with DNA, other, unidentified adducts, whichdid not apparently arise from reactions of this diol-epoxidewith DNA, were also present. Hydrocarbon — nucleosideadducts were not detected in hydrolysates of nucleic acids thatwere isolated from mouse skin that had been treated in vivowith DBA.