CHARACTERIZATION OF BENZO[A]PYRENE METABOLITES ISOLATED FROM MUSCLE, LIVER, AND BILE OF A JUVENILE FLATFISH
CHARACTERIZATION OF BENZO[A]PYRENE METABOLITES ISOLATED FROM MUSCLE, LIVER, AND BILE OF A JUVENILE FLATFISH
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DOI：
10.1093/carcin/3.12.1397
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发表时间：
1982-01-01
期刊：
影响因子：
4.7
通讯作者：
VARANASI, U
中科院分区：
文献类型：
--
作者：
GMUR, DJ;VARANASI, U
青少年英国唯一（P. vetulus）强制喂食[3 H]苯并[a]芘[致癌物]（BaP），24小时后，从胆汁，肝脏和肌肉中分离出代谢物。通过TLC和HPLC [高压液相色谱法]分析代谢产物，并通过UV、荧光或m.s. [mass光谱法]分析。BaP 7，8-二氢二醇、BaP 9，10-二氢二醇[（. ±.）反式-7，8-二氢-7，8-二羟基苯并（a）芘，（. ±.）-反式-9，10-二氢-9，10-二羟基苯并（a）芘]、1-羟基苯并（a）芘、3-羟基苯并（a）芘和9-羟基苯并（a）芘。胆汁中BaP 7，8-二氢二醇及其结合物（硫酸盐和葡萄糖醛酸苷）的量大于BaP 9，10-二氢二醇及其结合物的量的两倍。肝脏中含有的BaP 7，8-二氢二醇是BaP 9，10-二氢二醇的两倍，这表明英国鳎鱼产生了更大量的7，8-异构体。TLC分析显示存在未知代谢物X，其在BaP 9，10-和7，8-二氢二醇之间迁移。X被证明是苯并（a）芘的非邻位二羟基衍生物。X的光谱性质类似于那些报道的二羟基衍生物，大概是3，9-二羟基苯并[a]芘，形成从3-或9-羟基苯并[a]芘在大鼠肝微粒体的存在下。与二氢二醇相比，X对葡萄糖醛酸化和硫酸化都有抗性。形成水溶性代谢物的阻力可能是导致相对大量（给药剂量的0.11%）的X在肌肉中沉积的原因;肝脏中含有少量（0.01%）的X。英国鳎将BaP转化为已知对哺乳动物有毒的代谢物，这些代谢物在鱼的肝脏和可食用组织中发现。
Juvenile English sole (P. vetulus) were force fed [3H]benzo[a]pyrene [carcinogen] (BaP) and, after 24 h, metabolites were isolated from bile, liver and muscle. The metabolites were analyzed by TLC and HPLC [high pressure liquid chromatography], and further characterized by UV, fluorescence, or m.s. [mass spectrometry] analyses. The identities of BaP 7,8-dihydrodiol, BaP 9,10-dihydrodiol [(.+-.)-trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, (.+-.)-trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene, respectively], 1-hydroxy BaP, 3-hydroxy BaP and 9-hydroxy BaP were confirmed. The amounts of BaP 7,8-dihydrodiol plus its conjugates (sulfates and glucuronides) were greater than twice the amounts of BaP 9,10-dihydrodiol plus its conjugates in bile. Liver also contained twice as much BaP 7,8-dihydrodiol as BaP 9,10-dihydrodiol, demonstrating that English sole produced larger amounts of the 7,8-isomer. TLC analysis showed the presence of an unknown metabolite X migrating between BaP 9,10- and 7,8-dihydrodiols. X was shown to be a non-vicinal dihydroxy derivative of BaP. Spectral properties of X were similar to those reported for a dihydroxy derivative, presumably the 3,9-dihydroxy BaP, formed from either 3- or 9-hydroxy BaP in the presence of rat liver microsomes. Compared to the dihydrodiols, X was resistant to both glucuronidation and sulfation. The resistance to form water-soluble metabolites may be responsible for the deposition of relatively large amounts (0.11% of the administered dose) of X in muscle; liver contained a much smaller amount (0.01%) of X. English sole converted BaP into metabolites known to be toxic to mammals, and these metabolites were found in the liver and edible tissue of the fish.