Arzuaga Xabier, Elskus Adria
Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0225, USA.
Mar Environ Res. 2002 Sep-Dec;54(3-5):247-51. doi: 10.1016/s0141-1136(02)00184-8.
Halogenated aromatic hydrocarbons (HAHs) and polynuclear aromatic hydrocarbons (PAHs) are major environmental contaminants. Fish species that are chronically exposed to these compounds can develop resistance to their toxic effects. In all fish species studied to date, toxicant resistance has been accompanied by decreased inducibility of the xenobiotic metabolizing enzyme, cytochrome P450 1A (CYPIA). CYP1A induction is mediated through the Aryl Hydrocarbon Receptor (AHR). Although these compounds mediate their effects through this pathway, there have been resistant populations in which one chemical class cannot induce CYPIA expression (HAHs) while the other (PAHs) can. Resistance to PAHs was examined in a HAH-resistant population of Fundulus heteroclitus collected from a site contaminated with both compound classes (Newark Bay, NJ). Fish were injected intraperitoneally with the HAH 3,4,3',4'-tetrachlorobiphenyl (PCB77), benzo[a]pyrene (B[a]P, a PAH) or vehicle and sacrificed after 2 (B[a]P) or 5 days (PCB77, vehicle). We found no significant increase in CYP1A mRNA levels in resistant Newark Bay F. heteroclitus treated with either B[a]P or PCB77, while there was a 3.9 fold (PCB77) and 4.2 fold (B[a]P) increase in CYP1A mRNA in Flax fish relative to controls. AHR labeling studies revealed significantly (P < 0.05) lower levels of hepatic AHR in Newark fish (1,770 +/- 1,693.2 DPM) relative to Flax fish (6,082.5 +/- 1,709.9 DPM). Overall, these data suggest Newark F. heteroclitus are resistant to both PAHs and HAHs at the level of CYP1A mRNA, which might be mediated, in part, though lower expression of AHR. We are currently studying the promoter sequence to determine its role in chemical resistance.
卤代芳烃（HAHs）和多环芳烃（PAHs）是主要的环境污染物。长期接触这些化合物的鱼类会对其毒性作用产生抗性。在迄今为止研究的所有鱼类中，对毒物的抗性都伴随着外源性代谢酶细胞色素P450 1A（CYPIA）诱导性的降低。CYP1A的诱导是通过芳烃受体（AHR）介导的。尽管这些化合物通过该途径介导其作用，但存在一些抗性种群，其中一类化学物质（HAHs）不能诱导CYPIA表达，而另一类（PAHs）可以。在从同时受这两类化合物污染的地点（新泽西州纽瓦克湾）采集的抗HAH的异鳞鳉种群中检测了对PAHs的抗性。给鱼腹腔注射卤代芳烃3,4,3',4'-四氯联苯（PCB77）、苯并[a]芘（B[a]P，一种多环芳烃）或溶剂，在注射2天（B[a]P）或5天（PCB77、溶剂）后处死。我们发现，用B[a]P或PCB77处理过的抗HAH的纽瓦克湾异鳞鳉中，CYP1A mRNA水平没有显著增加，而相对于对照组，亚麻鱼中的CYP1A mRNA分别增加了3.9倍（PCB77）和4.2倍（B[a]P）。AHR标记研究显示，纽瓦克鱼肝脏中的AHR水平（1,770±1,693.2 DPM）显著低于（P<0.05）亚麻鱼（6,082.5±1,709.9 DPM）。总体而言，这些数据表明，纽瓦克异鳞鳉在CYP1A mRNA水平上对PAHs和HAHs都具有抗性，这可能部分是由AHR表达降低介导的。我们目前正在研究启动子序列，以确定其在化学抗性中的作用。
