Comparative metabolism of benzo(a)pyrene and covalent binding to hepatic DNA in English sole, starry flounder, and rat.
Comparative metabolism of benzo(a)pyrene and covalent binding to hepatic DNA in English sole, starry flounder, and rat.
复制标题
英国鳎鱼、星鲽鱼和大鼠中苯并(a)芘的代谢比较以及与肝 DNA 的共价结合。
作者：
U. Varanasi;M. Nishimoto;William L. Reichert;B.
使用两种底栖鱼类：英国鳎鱼 (Parophrys vetulus) 和星鲽 (Platichthys stellatus) 以及 Sprague-Dawley 大鼠，研究了苯并 (a) 芘 (BaP) 的体内和体外代谢。给鱼口服 BaP（7.9 微摩尔/千克体重）后 24 小时，或者口服。 （实验 1）或 i.p. （实验2），BaP代谢物与肝DNA结合的比活性（每毫克DNA的pmol BaP当量）在鞋底中较高[实验1中的2.1；实验 2 中的 28 +/- 5 (SE)] 比比目鱼（实验 1 中的 0.5；实验 2 中的 14 +/- 4）要高。在两个实验中，用 β-葡萄糖醛酸酶和芳基硫酸酯酶处理胆汁，从鳎鱼胆汁中释放出的 7,8-二羟基-7,8-二氢-BaP（BaP 7,8-二醇）比例显着高于比目鱼胆汁中的比例。然而，两种鱼类的 BaP 代谢速率和肝微粒体形成 BaP 7,8-二醇的速率相当。因此，暴露于 BaP 的鲽鱼和比目鱼胆汁中 DNA 结合水平和 BaP 7,8-二醇浓度的差异显然是由于 BaP 7,8-氧化物和 BaP 7,8-二醇-9,10-环氧化物的解毒而不是形成的差异所致。大鼠肝微粒体形成 BaP 7,8-二醇的速率（每毫克蛋白质每分钟形成 28 +/- 1 pmol BaP 7,8-二醇）与两种鱼类的肝微粒体（鳎鱼为 50 +/- 10，比目鱼为 33 +/- 6）相当，尽管 BaP 代谢速率（600 +/- 200）大约是鱼类的 3 倍（鳎目鱼为 190 +/- 60，比目鱼为 180 +/- 40）。因此，与大鼠相比，鱼类的肝微粒体将更大比例的 BaP 转化为 BaP 7,8-二醇。 BaP 体外代谢的这些差异部分有助于解释 BaP 暴露大鼠中肝 DNA 的结合（0.3 +/- 0.1；实验 2）显着低于鳎目鱼或比目鱼。
Metabolism of benzo(a)pyrene (BaP) in vivo and in vitro was studied using two benthic fish species, English sole (Parophrys vetulus) and starry flounder (Platichthys stellatus), and Sprague-Dawley rats. At 24 h after administration of BaP (7.9 mumol/kg of body weight) to fish either p.o. (Experiment 1) or i.p. (Experiment 2), the specific activity of binding of BaP metabolites to hepatic DNA (pmol of BaP equivalent per mg of DNA) was higher in sole [2.1 in Experiment 1; 28 +/- 5 (SE) in Experiment 2] than in flounder (0.5 in Experiment 1; 14 +/- 4 in Experiment 2). Treatment of bile with beta-glucuronidase and arylsulfatase released a significantly higher proportion of 7,8-dihydroxy-7,8-dihydro-BaP (BaP 7,8-diol) from sole bile than from flounder bile in both experiments. However, the rate of BaP metabolism and rate of formation of BaP 7,8-diol by hepatic microsomes were comparable for both fish species. Thus, the differences in both the level of DNA binding and the concentration of BaP 7,8-diol in bile of BaP-exposed sole and flounder were apparently due to differences in detoxication, rather than formation, of BaP 7,8-oxide and BaP 7,8-diol-9,10-epoxide. The rate of formation of BaP 7,8-diol by rat liver microsomes (28 +/- 1 pmol of BaP 7,8-diol formed per min per mg of protein) was comparable to that by hepatic microsomes from both fish species (50 +/- 10 for sole and 33 +/- 6 for flounder), although the rate of BaP metabolism (600 +/- 200) was approximately 3 times greater than that by the fish species (190 +/- 60 for sole and 180 +/- 40 for flounder). Thus, greater proportion of BaP was converted to BaP 7,8-diol by liver microsomes of fish species than rat. These differences in BaP metabolism in vitro help explain, in part, the substantially lower binding (0.3 +/- 0.1; Experiment 2) for hepatic DNA in BaP-exposed rat than that in either sole or flounder.
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