Altered CYP1A expression in Fundulus heteroclitus adults and larvae:: a sign of pollutant resistance?
Altered CYP1A expression in Fundulus heteroclitus adults and larvae:: a sign of pollutant resistance?
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DOI：
10.1016/s0166-445x(98)00102-7
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发表时间：
1999-04-01
影响因子：
4.5
通讯作者：
Woltering, DS
中科院分区：
文献类型：
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作者：
Elskus, AA;Monosson, E;Woltering, DS
本研究探讨了在高度污染的纽瓦克湾，新泽西州的一个人口的底栖动物的CYP 1A诱导的耐药性的发展。CYP 1A是P450单加氧酶，其表达在脊椎动物中由许多有机污染物诱导，包括多氯联苯（PCB）。CYP 1A在高污染人群中的表达降低可能代表对化学应激源的抗性。成年F.将来自纽瓦克湾和参考地点异石藻在清洁海水中保持6个月，以使它们净化其污染物身体负荷。这些鱼，然后暴露于一个单一的多氯联苯在配子发生和CYP 1A的表达在父母和幼虫测量腹腔注射。孵化成功率，幼虫存活率和幼虫生长也进行了测量，没有效果的PCB治疗观察到这些参数。来自参考种群的鱼对PCB处理表现出强烈的CYP 1A剂量反应。用0、10或100毫克多氯联苯处理的参考成年男性（kg体重）（-1）的肝乙氧基试卤灵O-脱乙基酶（EROD）活性分别为132 +/- 46.1、43.3 +/- 59.5和345.4 +/- 197.5 pmol min（-1）mg（-1），CYP 1A蛋白水平为7 +/- 5.6;注射后7周时为6.1 +/- 4.8和92.6 +/- 25 pmol mg（-1）（平均值+/- SD）。CYP 1A的表达在24小时和8天后孵化的幼虫从多氯联苯处理的参考父母进行了化学计量，并揭示了一个强大的和持久的诱导剂量相关。此外，幼虫器官依次响应增加父母PCB剂量在以下顺序：肝细胞，鳃，肠道和心脏;肾脏似乎表达CYP 1A constitutional。与参考鱼相反，纽瓦克湾的成年鱼和幼虫没有表现出诱导CYP 1A的任何PCB治疗。这些结果表明，纽瓦克湾人群对CYP 1A诱导剂的反应发生了改变，这种改变既具有持久性，又可能具有遗传性，在慢性或极端暴露条件下，使用CYP 1A作为生物标志物可能会产生误导，并强调需要精心设计研究，将CYP 1A以外的指标用作暴露或效应的生物标志物。(C)1999 Elsevier Science B. V.保留所有权利。
This study addresses the development of resistance to CYP1A induction in a population of Fundulus heteroclitus from highly contaminated Newark Bay, NJ. CYP1A is a P450 monooxygenase whose expression is induced in vertebrates by numerous organic contaminants, including polychlorinated biphenyls (PCBs). Reduced expression of CYP1A in highly contaminated populations may represent resistance to chemical stressors. Adult F. heteroclitus from Newark Bay and a reference site were held in clean seawater for 6 months to allow them to depurate their contaminant body burdens. These fish were then exposed to a single intraperitoneal injection of PCBs during gametogenesis and CYP1A expression measured in parents and larvae. Hatching success, larval survival and larval growth were also measured; no effect of PCB treatment was observed in these parameters. Fish from the reference population exhibited a strong CYP1A dose-response to PCB treatments. Reference adult males treated with 0, 10 or 100 mg PCB (kg body weight)(-1) had hepatic ethoxyresorufin O-deethylase (EROD) activities of 132 +/- 46.1, 43.3 +/- 59.5 and 345.4 +/- 197.5 pmol min(-1) mg(-1), respectively, and CYP1A protein levels of 7 +/- 5.6; 6.1 +/- 4.8 and 92.6 +/- 25 pmol mg(-1) (means +/- SD) at 7 weeks post-injection. CYP1A expression in 24-h and 8-day post-hatch larvae from PCB-treated reference parents was measured immunohistochemically and revealed a strong and persistent induction that was dose-related. Further, larval organs responded sequentially to increasing parental PCB dose in the following order: hepatocytes, gill, gut and heart; the kidney appeared to express CYP1A constituitively. In contrast to the reference fish, Newark Bay adults and larvae failed to show induction of CYP1A in response to any PCB treatment. These results indicate that the Newark Bay population has acquired an altered response to CYP1A inducers that is both persistent and possibly heritable, that use of CYP1A as a biomarker may be misleading under conditions of chronic or extreme exposure, and emphasize the need for carefully designed studies which employ indicators in addition to CYP1A as biomarkers of exposure or effects. (C) 1999 Elsevier Science B.V. All rights reserved.