Sorrentino C, Roy N K, Courtenay S C, Wirgin I
Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
Aquat Toxicol. 2005 Nov 10;75(3):238-52. doi: 10.1016/j.aquatox.2005.08.006. Epub 2005 Sep 23.
Populations from urbanized and industrialized sites are often exposed to mixtures of chemical contaminants including aromatic hydrocarbons (AHs) and heavy metals. The effects of mixtures of these contaminants on these populations are largely unknown. The Hudson River Estuary is highly contaminated with a variety of AHs including, PCBs and PAHs, and metals, and its population of Atlantic tomcod Microgadus tomcod bioaccumulates those which are persistent. The Hudson River's tomcod population exhibits resistance to persistent AHs as exemplified by significantly decreased inducibility of hepatic cytochrome P4501A (CYP1A) mRNA. We used hepatic CYP1A mRNA inducibility in tomcod from the Hudson River and a sensitive population to investigate the effects of acute co-exposure to metals on aryl hydrocarbon receptor (AHR)-mediated gene expression. Adult tomcod from the Hudson River and the cleaner Miramichi River were i.p. injected with one dose of benzo[a]pyrene (B[a]P) or coplanar PCB77 and graded doses of four metals, As, Cd, Cr, and Ni, and levels of hepatic CYP1A mRNA and protein were assayed. We observed no effects of metals treatment on basal levels of hepatic CYP1A mRNA expression, but all four metals significantly reduced CYP1A mRNA inducibility in tomcod from one or both populations. The magnitude of the inhibition of CYP1A mRNA inducibility differed among the metals and fish from the two populations. Also, the profile of the metals modulation of induced CYP1A mRNA showed differences that depended on the time after treatment of sacrifice. Our results demonstrate that co-exposure to several metals can impact inducible, but not basal levels of CYP1A expression and perhaps other toxicities mediated by the AHR.
城市化和工业化地区的人群常常暴露于包括芳烃（AHs）和重金属在内的化学污染物混合物中。这些污染物混合物对这些人群的影响在很大程度上尚不清楚。哈德逊河河口受到多种AHs（包括多氯联苯和多环芳烃）以及金属的高度污染，其大西洋小鳕种群会生物累积那些持久性污染物。哈德逊河的小鳕种群对持久性AHs表现出抗性，例如肝细胞色素P4501A（CYP1A）mRNA的诱导性显著降低。我们利用哈德逊河小鳕和一个敏感种群的肝细胞CYP1A mRNA诱导性，来研究急性共同暴露于金属对芳烃受体（AHR）介导的基因表达的影响。从哈德逊河和较清洁的米拉米奇河采集成年小鳕，腹腔注射一剂苯并[a]芘（B[a]P）或共平面多氯联苯77以及四种金属（砷、镉、铬和镍）的分级剂量，然后检测肝细胞CYP1A mRNA和蛋白质水平。我们观察到金属处理对肝细胞CYP1A mRNA表达的基础水平没有影响，但所有四种金属都显著降低了来自一个或两个种群的小鳕中CYP1A mRNA的诱导性。两种群小鳕中，不同金属对CYP1A mRNA诱导性的抑制程度有所不同。此外，金属对诱导的CYP1A mRNA的调节模式也显示出差异，这取决于处理后至处死的时间。我们的结果表明，共同暴露于几种金属会影响CYP1A表达的诱导水平，但不影响基础水平，可能还会影响由AHR介导的其他毒性。
