Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.
Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.
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DOI：
10.1289/ehp.0901799
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发表时间：
2010-10
影响因子：
10.4
通讯作者：
Di Giulio RT
中科院分区：
文献类型：
--
作者：
Wills LP;Jung D;Koehrn K;Zhu S;Willett KL;Hinton DE;Di Giulio RT
弗吉尼亚州朴次茅斯伊丽莎白河 (ER) 上的大西洋木材工业超级基金基地受到来自杂酚油的多环芳烃 (PAH) 污染。 ER 鳉鱼 (Fundulusheteroclitus) 的胚胎和幼虫对由芳基烃受体调节的酶（包括细胞色素 P4501A (CYP1A)）的诱导具有抵抗力，并且对 PAH 诱导的致死性和致畸性具有抵抗力。然而，与参考地点的相比，成年 ER 鳉鱼的肝脏和胰腺肿瘤患病率更高。我们使用对照实验室研究来确定 ER 鳉鱼对 PAH 引起的慢性肝毒性是否比来自未污染地点的鳉鱼更敏感或更不敏感。来自 ER 和 King’s Creek (KC) 参考地点的幼虫接受了两次 24 小时的苯并[a]芘（BaP；0–400 μg/L）水溶液暴露。在不同的时间点，对幼虫的 CYP1A 活性、BaP 浓度、核和线粒体 DNA 损伤以及肝脏病理学进行分析。 KC 幼虫中的 CYP1A 活性是由 BaP 诱导的，而 ER 幼虫则不然，并且 KC 幼虫的全身 BaP 浓度随着时间的推移表现出更大的降低。 BaP 暴露的 KC 幼虫中线粒体和核 DNA 损伤频率显着增加，但 ER 幼虫中则没有。暴露后九个月，KC 幼体表现出明显更多的肝细胞改变灶，并且只有 KC 幼体发展为肝细胞癌。除了获得对多环芳烃急性致畸作用的遗传抵抗力外，ER 鱼似乎还对慢性影响（包括癌症）产生了抵抗力。
The Atlantic Wood Industries Superfund site on the Elizabeth River (ER) in Portsmouth, Virginia, is contaminated with polycyclic aromatic hydrocarbons (PAHs) derived from creosote. Embryos and larvae of ER killifish (Fundulus heteroclitus) are refractory to the induction of enzymes regulated by the aryl hydrocarbon receptor including cytochrome P4501A (CYP1A) and are resistant to PAH-induced lethality and teratogenicity. However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites. We used controlled laboratory studies to determine if ER killifish are more or less sensitive to PAH-induced chronic hepatic toxicity than killifish from an uncontaminated site. Larvae from the ER and a reference site on King’s Creek (KC) were subjected to two 24-hr aqueous exposures of benzo[a]pyrene (BaP; 0–400 μg/L). At various time points, larvae were analyzed for CYP1A activity, BaP concentrations, nuclear and mitochondrial DNA damage, and liver pathology. CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time. Mitochondrial and nuclear DNA lesion frequency increased significantly in BaP-exposed KC larvae, but not in ER larvae. Nine months postexposure, KC juveniles exhibited significantly more hepatic foci of cellular alteration and only KC juveniles developed hepatocellular carcinomas. In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.
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DOI：
10.1016/j.cbpc.2008.07.007
发表时间：
2009-03-01
影响因子：
3.9
作者：
Jung, Dawoon;Cho, Youngeun;Di Giulio, Richard T.
通讯作者：
Di Giulio, Richard T.
影响因子：
9.8
作者：
BAUMANN, PC;HARSHBARGER, JC;HARTMAN, KJ
通讯作者：
HARTMAN, KJ
影响因子：
4.1
作者：
Meyer, JN;Wassenberg, DM;Di Giulio, RT
通讯作者：
Di Giulio, RT
影响因子：
5
作者：
Gallant, AL;Hansen, AJ;Betz, DW
通讯作者：
Betz, DW
影响因子：
4.5
作者：
MALINS, DC;MCCAIN, BB;ROUBAL, WT
通讯作者：
ROUBAL, WT