The metabolic and activation of dibenz[a,c]anthracene

In rat liver microsomal preparations, the 10,11-dihydrodiol of dibenz[a,c]anthracene (DBA) is metabolized to r-10,t-11-dihydroxy-t-12,13-oxy-10,11,12,13-tetrahydrodibenz[a,c]anthracene (anti-DBA 10,11-diol 12,13-oxide), the anti isomer of a non-bay-region diol-epoxide of DBA. When 3H-labelled DBA or trans-10,11-dihydro-10,11-dihydroxydibenz[a,c]anthracene were metabolized in this system in the presence of DNA or when 3H-labelled DBA was added to primary cultures of hamster embryo cells, covalent reactions of hydrocarbon metabolites with DNA occurred. The chromatographic characteristics of the radioactive hydrocarbon-deoxyribonucleoside adducts formed in these reactions were examined using Sephadex LH20 column chromatography and high pressure liquid chromatography. The results showed that whilst some of the radioactive hydrocarbon-deoxyribonucleoside adducts formed were indistinguishable from adducts that were formed when anti-DBA 10,11-diol 12,13-oxide reacted with DNA, other, unidentified adducts, which did not apparently arise from reactions of this diol-epoxide with DNA, were also present. Hydrocarbon-nucleoside adducts were not detected in hydrolysates of nucleic acids that were isolated from mouse skin that had been treated in vivo with DBA.