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虹鳟(Oncorhynchus mykiss)离体肝细胞中五氯苯酚、苯胺和联苯的生物转化:与体内代谢的比较

Biotransformation of pentachlorophenol, aniline and biphenyl in isolated rainbow trout (Oncorhynchus mykiss) hepatocytes: comparison with in vivo metabolism.

作者信息

Cravedi J P, Lafuente A, Baradat M, Hillenweck A, Perdu-Durand E

机构信息

Laboratoire des Xénobiotiques, INRA, Toulouse, France.

出版信息

Xenobiotica. 1999 May;29(5):499-509. doi: 10.1080/004982599238506.

Abstract
  1. The biotransformation of pentachlorophenol (PCP), aniline and biphenyl in rainbow trout (Oncorhynchus mykiss) isolated liver cells was investigated to examine if fish hepatocytes represent a suitable alternative to the in vivo approach for studying the biotransformation of chemicals. Each compound was incubated at two concentrations (10 and 60 microM) for 2 h. For comparison, the metabolic profile of these xenobiotics was also studied in urine and bile of trout orally exposed to 1.8-4.0 mg/kg wet wt of each compound. 2. In vitro as in vivo, PCP glucuronide and to a lesser extent PCP sulphate were the metabolites formed by trout from PCP. 3. Aniline was mainly metabolized to acetanilide and to a lesser extent to 2-aminophenol by isolated hepatocytes, but neither hydroxylated acetanilide nor conjugates were found in vitro whereas they were present in bile and urine of trout treated with this chemical. 4. Trout hepatocytes metabolized biphenyl to hydroxylated and dihydroxylated products and the corresponding glucuronides. These results correlated well with the metabolic profile obtained from the bile of trout exposed to this pesticide. 5. It is concluded that although hepatocytes are well suited for several types of biotransformation studies, the fact that this system may in some cases produce a different metabolic pattern than in vivo should be considered when attempting to extrapolate in vitro to in vivo data.
摘要
  1. 研究了虹鳟(Oncorhynchus mykiss)分离肝细胞中五氯苯酚(PCP)、苯胺和联苯的生物转化,以检验鱼类肝细胞是否是研究化学物质生物转化的体内方法的合适替代方案。每种化合物在两种浓度(10和60微摩尔)下孵育2小时。为作比较,还研究了口服暴露于每种化合物1.8 - 4.0毫克/千克湿重的虹鳟尿液和胆汁中这些外源化合物的代谢谱。2. 与体内情况一样,PCP葡萄糖醛酸苷以及程度稍低的PCP硫酸盐是虹鳟由PCP形成的代谢产物。3. 苯胺主要被分离的肝细胞代谢为乙酰苯胺,程度稍低地代谢为2 - 氨基酚,但在体外未发现羟基化乙酰苯胺或共轭物,而在用该化学物质处理的虹鳟的胆汁和尿液中则有这些物质。4. 虹鳟肝细胞将联苯代谢为羟基化和二羟基化产物以及相应的葡萄糖醛酸苷。这些结果与从暴露于该农药的虹鳟胆汁中获得的代谢谱密切相关。5. 得出的结论是,尽管肝细胞非常适合几种类型的生物转化研究,但在试图将体外数据外推至体内数据时,应考虑到该系统在某些情况下可能产生与体内不同的代谢模式这一事实。

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