Metabolism of dibenz[a,h]acridine by rat liver microsomes.
Metabolism of dibenz[a,h]acridine by rat liver microsomes.
复制标题
大鼠肝微粒体对二苯并[a,h]吖啶的代谢。
DOI：
10.1093/carcin/8.8.1043
复制
发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Sikka,HC
中科院分区：
文献类型：
--
作者：
Steward,AR;Kumar,S;Sikka,HC
As part of a project to assess the effect of heterocyclic nitrogen in modifying the metabolism and mutagenicity of polycyclic aromatic hydrocabons, we investigated the metabolism of dibenz[a,h]acridine (DB[a,h]AC) by liver microsomes prepared from male Sprague-Dawley rats. During a 6-min incubation 21, 14, 0.7 or 0.2 nmol DB[a,h]AC per mg protein were metabolized by microsomes from rats pre-treated with DB[a,h]AC, 3-methylcholanthrene (3-MC), phenobarbital (PB) or corn oil, respectively. In each case the predominant metabolites were the dihydrodiols with bay-region double bonds, namely, DB[a,h]AC-3,4-dihydrodiol and DB[a,h]AC-10,11-dihydrodiol, each of which accounted for 21–23% of the total metabolism determined during a 7-min incubation with microsomes from 3-MC-treated rats. Other metabolites produced by these microsomes included DB[a,h]AC-l,2-dihydrodiol (˜5% of total metabolites); two K-region oxides [DB[a,h]AC-12,13- and 5,6-oxides (estimated to represent 5% and 2% of total metabolites, respectively)]; several unidentified polar metabolites (10–15%) and several unidentified metabolites which co-eluted with 3-hydroxy-DB[a,h]AC (20%). DB[a,h]AC-8,9-dihydrodiol was not detected (<2%). The metabolite profiles produced by microsomes prepared from rats pretreated with DB[a,h]AC, PB or corn oil were very similar to the profile produced by 3-MC-induced microsomes. We conclude that: (i) the potentially mutagenic benzo-ring dihydrodiols with bay-region double bonds are the predominant metabolite of DB[a,h]AC; (ii) the heterocyclic nitrogen atom has little effect in modifying the relative extents of formation of these two benzo-ring dihydrodiols with bay-region double bonds; (iii) metabolism at the K-region is only a minor pathway for DB[a,h]AC, as is also true for the carbon analogue dibenz[a,h]anthracene; and (iv) induction by a 3-MC-type inducer (e.g. DB[a,h]AC) is required for substantial metabolism to occur.
