Comparative metabolism and excretion of benzo(a)pyrene in 2 species of ictalurid catfish.

Comparative metabolism and excretion of benzo(a)pyrene in 2 species of ictalurid catfish.
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两种鮰鱼中苯并(a)芘的代谢和排泄比较。

DOI:
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发表时间:
2000
影响因子:
3.8
通讯作者:
R. Di Giulio
R. Di Giulio
中科院分区:
医学2区
文献类型:
--
作者:
K. Willett;P. Gardinali;L. A. Lienesch;R. Di Giulio

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多环芳烃(PAH)介导的肝癌易感性在两个亲缘物种中存在差异。本研究提出了两个假设来解释这种差异。具体来说,相对不敏感的通道鲶鱼1)不会产生致突变的多环芳烃代谢物,和/或2)由于II期酶活性更高,它们比更敏感的棕色牛头鱼更快地消除多环芳烃。在单次接触10 mg/kg的苯并(a)芘(BaP)后6、24、72和168 h采集肝脏和胆汁。BaP处理对两种植物胞质1-氯-2,4-二硝基苯或乙酸(EA)-谷胱甘肽-s -转移酶(GST)和顺式二苯乙烯氧化物-微粒体环氧化物水解酶(EH)活性均无显著影响。通道鲶鱼EH和GST活性分别比褐头鱼高1.2倍(p = 0.058和p < 0.002)。用HPLC-APCI-MS对提取的胆汁和酶解的胆汁进行葡萄糖醛酸转移酶(GT)、GST和硫代转移酶(ST)结合的代谢物检测,结果表明在消除总胆道代谢物方面没有物种差异。GT共轭占优;ST和GST共轭最小。在这两个物种中,bap -二酮占代谢物的大部分。总的来说,这些结果表明,棕色牛头鱼优先形成bap -7,8-二氢二醇,这是dna反应性bap -7,8-二氢二醇-9,10-环氧化物(BPDE)的前体,这可能与该物种对多环芳烃的敏感性增加有关。
Differential susceptibility of polycyclic aromatic hydrocarbon (PAH)-mediated liver cancer exists in two related species of Ictalurid catfish. Two hypotheses are addressed in this study to explain this difference. Specifically, the relatively insensitive channel catfish 1) do not produce mutagenic PAH metabolites, and/or 2) they more quickly eliminate PAHs due to greater Phase II enzyme activities than the more sensitive brown bullhead. Livers and bile were collected from each species 6, 24, 72, and 168 h after a single 10 mg/kg i.p. benzo(a)pyrene (BaP) exposure. BaP treatment had no significant effect on cytosolic 1-chloro-2,4-dinitrobenzene or ethacrynic acid (EA)-glutathione-S:- transferase (GST) and cis-stilbene oxide-microsomal epoxide hydrolase (EH) activities of either species. Channel catfish EH and GST activities were 1.2-fold higher than brown bullhead activities (p = 0.058 and p < 0.002, respectively). HPLC-APCI-MS of extracted bile and bile enzymatically digested to detect glucuronyl transferase (GT), GST, and sulfotransferase (ST) conjugated metabolites indicated no species differences in elimination or profiles of total biliary metabolites. GT conjugates predominated; ST and GST conjugates were minimal. BaP-diones accounted for the majority of metabolites in both species. Overall, these results indicated that brown bullhead preferentially formed BaP-7,8-dihydrodiol, a precursor to the DNA-reactive BaP-7, 8-dihydrodiol-9,10-epoxide (BPDE), which may be linked to the increased PAH susceptibility in this species.
DOI: 10.1021/tx990028s
发表时间: 1999-07-01
影响因子: 4.1
作者:
Shimada, T;Gillam, EMJ;Inoue, K
通讯作者: Inoue, K