Fuchs J, Mlcoch J, Oesch F, Platt K L
Institute of Toxicology, University of Mainz, Federal Republic of Germany.
Toxicol Ind Health. 1993 May-Jun;9(3):503-9. doi: 10.1177/074823379300900309.
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,11S-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 pmol/mg 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 predominant adducts in vitro.
在从用多氯联苯混合物1254预处理的雄性斯普拉格-道利大鼠分离的肝微粒体对3,4,10,11-四羟基-3,4,10,11-四氢二苯并[a,h]蒽（二苯并[a,h]蒽-3,4,10,11-双二醇）进行代谢活化后，发现了两种高度极性的DNA加合物，小牛胸腺DNA存在时。这些DNA加合物可归属于二苯并[a,h]蒽（DBA）、3R,4R,10R,11R-四羟基-3,4,10,11-四氢-DBA和3R,4R,10S,11S-四羟基-3,4,10,11-四氢-DBA的代谢产物。未发现源自3S,4S,10S,11S-四羟基-3,4,10,11-四氢-DBA代谢产物的DNA加合物。在用活化系统使二苯并[a,h]蒽、3R,4R-二羟基-3,4-二氢-DBA（(-)-二苯并[a,h]蒽-3,4-二醇）和3S,4S-二羟基-3,4-二氢-DBA（(+)-二苯并[a,h]蒽-3,4-二醇）与DNA孵育后，这些高度极性的加合物也可用反相高效液相色谱法检测到。在用14C标记的二苯并[a,h]蒽孵育后，发现源自二苯并[a,h]蒽-3,4,10,11-双二醇的DNA加合物占比为38%，而湾区3,4-二羟基-1,2-环氧-1,2,3,4-四氢-DBA-DNA加合物的水平为25%。二苯并[a,h]蒽-3,4,10,11-双二醇表现出比(-)-二苯并[a,h]蒽-3,4-二醇（23±6 pmol/mg DNA）更高的DNA结合产率（38±12 pmol/mg DNA），(-)-二苯并[a,h]蒽-3,4-二醇是最具致突变性的3,4-二醇对映体。对于(+)-二苯并[a,h]蒽-3,4-二醇，源自二苯并[a,h]蒽-3,4,10,11-双二醇的高度极性DNA加合物是迄今为止体外最主要的加合物。
