Characterization of Highly Polar Dna Adducts Derived from Dibenz[A,H]Anthracene (DBA),3,4-Dihydroxy-3,4-Dihydro-DBA,and 3,4,10,11-Tetrahydroxy-3,4,10,11-Tetrahydro-DBA

Abstract

Two highly polar DNA adducts were found after metabolic activation of 3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydrodibenz[a,h]anthracene(DBA-3,4;10, 11-bisdiol) by liver microsomes isolated from male Sprague-Dawley rats pretreated with Aroclor 1254 in presence of calf thymus DNA. These DNA adducts could be assigned to the metabolites of dibenz[a,h]anthracene (DBA), of 3R,4R,10R,11R-tetrahydroxy-3,4,10,11-tetrahydro-DBA and of 3R,4R,10S,US-tetrahydroxy-3,4,10,11-tetrahydro-DBA. DNA adducts derived from metabolites of 3S,4S,10S,11S-tetrahydroxy-3,4,10,11-tetrahydro-DBA were not found.

These highly polar adducts also could be detected by reversed phase HPLC after incubation of dibenz[a,h]anthracene, 3R,4R-dihydroxy-3,4-dihydro-DBA ((-)-DBA-3,4-diol) and 3S,4S- dihydroxy-3,4-dihydro-DBA ((+)-DBA-3,4-diol) with DNA in presence of the activating system. After incubation of ¹⁴C labelled DBA DNA adducts derived from DBA-3,4;10,11-bisdiol were found in a fraction of 38% and bay region 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydro-DBA-DNA adducts at a level of 25%. DBA-3,4; 10,11-bisdiol exhibited a higher DNA binding yield (38 × 12 pmollmg DNA) than (-)-DBA-3,4-diol (23 × 6 pmol/mg DNA), the most mutagenic 3,4-diol enantiomer. For (+)-DBA-3,4-diol the highly polar DNA adducts derived from DBA-3,4;10,11-bisdiol were by far the most predotmnant adducts in vitro.

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