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食蚊鱼(Poeciliopsis monacha)和露西食蚊鱼(Poeciliopsis lucida)对苯并[a]芘的摄取、毒性、分布及单加氧酶诱导作用

Uptake, toxicity, and distribution of benzo[a]pyrene and monooxygenase induction in the topminnows Poeciliopsis monacha and Poeciliopsis lucida.

作者信息

Goddard K A, Schultz R J, Stegeman J J

机构信息

Biology Department, Woods Hole Oceanographic Institution, MA 02543.

出版信息

Drug Metab Dispos. 1987 Jul-Aug;15(4):449-55.

PMID:2888615
Abstract

Poeciliopsis lucida and Poeciliopsis monacha are freshwater viviparous fishes susceptible to tumorigenesis by brief exposure to waterborne procarcinogens. The hepatic monooxygenase system and the uptake, toxicity, and distribution of benzo[a]pyrene (BP) were characterized as a first step in exploring relationships between xenobiotic metabolism and cancer in these fishes. Waterborne BP was lethal at a dose of 3.75 mg/liter with a 24-hr exposure. During a 24-hr exposure to 1.0 mg/liter (3.97 mumol/liter) [3H]BP, an average of 8.27 nmol of BP was taken up per fish. Of this total, 64-70% was in the gallbladder or gut, indicating rapid metabolism and excretion. Basal levels of aryl hydrocarbon hydroxylase (AHH) activity were fairly high, about 0.6 nmol/min/mg. Maximal induction by BP occurred at a dose of 1.0 mg/liter, but with AHH activities only about twice the levels in untreated fish. Sensitivity to inhibition by alpha-naphthoflavone (ANF) increased slightly in treated fish. Induced AHH and also 7-ethoxyresorufin O-deethylase (EROD) activities declined slowly after a single treatment, approaching pre-exposure levels after 7 days. Monoclonal and polyclonal antibodies to cytochrome P-450E, the AHH and EROD catalyst in the marine fish scup (Stenotomus chrysops), inhibited AHH and EROD activities in untreated Poeciliopsis, indicating structural similarity between the catalysts in these fish species. Untreated Poeciliopsis evidently contain a counterpart to scup cytochrome P-450E, the major polycyclic aromatic hydrocarbon-inducible from in scup. High levels of basal activity and the pattern of monooxygenase induction could be involved in the sensitivity of these fishes to polycyclic aromatic hydrocarbon and other procarcinogens.

摘要

亮背食蚊鱼和莫氏食蚊鱼是淡水胎生鱼类,短暂接触水中的致癌物就易发生肿瘤。作为探索这些鱼类中异生物质代谢与癌症之间关系的第一步,对肝脏单加氧酶系统以及苯并[a]芘(BP)的摄取、毒性和分布进行了表征。在24小时暴露时,水中BP剂量为3.75毫克/升是致死的。在24小时暴露于1.0毫克/升(3.97微摩尔/升)的[3H]BP期间,每条鱼平均摄取8.27纳摩尔的BP。在这一总量中,64 - 70%存在于胆囊或肠道中,表明代谢和排泄迅速。芳烃羟化酶(AHH)活性的基础水平相当高,约为0.6纳摩尔/分钟/毫克。BP在1.0毫克/升的剂量下诱导作用最大,但诱导后的AHH活性仅约为未处理鱼的两倍。处理后的鱼对α - 萘黄酮(ANF)抑制的敏感性略有增加。单次处理后,诱导的AHH以及7 - 乙氧基异吩恶唑酮 - O - 脱乙基酶(EROD)活性缓慢下降,7天后接近暴露前水平。针对海洋鱼类条纹鲈(Stenotomus chrysops)中AHH和EROD的催化剂细胞色素P - 450E的单克隆和多克隆抗体,抑制了未处理的食蚊鱼中的AHH和EROD活性,表明这些鱼类中的催化剂在结构上具有相似性。未处理的食蚊鱼显然含有与条纹鲈细胞色素P - 450E相对应的物质,条纹鲈细胞色素P - 450E是条纹鲈中主要的多环芳烃诱导物。基础活性水平高以及单加氧酶的诱导模式可能与这些鱼类对多环芳烃和其他致癌物的敏感性有关。

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