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细胞色素P4501A诱导的鸡胚血管内皮细胞中苯并[a]芘和7,12-二甲基苯并[a]蒽加合物的形成。

Formation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene adducts in vascular endothelia of cytochrome P4501A-induced chicken embryos.

作者信息

Granberg Lizette, Brunström Björn, Brandt Ingvar

机构信息

Department of Environmental Toxicology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18 A, SE-752 36 Uppsala, Sweden.

出版信息

Environ Toxicol Chem. 2003 Oct;22(10):2393-9. doi: 10.1897/02-420.

DOI:10.1897/02-420
PMID:14552004
Abstract

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and birds may be exposed to PAHs via diet, from preening feathers contaminated with oil, or through contamination of the eggshell during embryo development. In the present study, tissue distribution and the cell-specific binding of two labeled PAHs, benzo[a]pyrene ([3H]BaP) and 7,12-dimethylbenz[a]anthracene ([3H]DMBA), were examined in chicken embryos exposed in ovo to CYP1A inducers. Tape-section autoradiograms revealed high concentrations of radioactivity in the bile, liver, kidneys, heart, and leptomeninges. Light microscopy autoradiography of solvent-extracted tissue slices showed a high and selective binding in endothelial cells in certain blood vessels in brain, heart, lung, and chest muscle. Binding was also observed in blood vessel endothelial cells in the chorioallantoic membrane (CAM), an extraembryonal tissue lining the eggshell. Endothelial binding was confirmed in CAM exposed in vitro, implying that tissue-binding metabolites were formed in situ. The CYP1A inhibitor ellipticine abolished bleeding in the target endothelial cells in CAM. It is thus concluded that blood vessel endothelia in various tissues in birds can bioactivate environmental contaminants and be targets for their toxicity. In view of its critical position beneath the shell, the CAM could be an important target for toxicants following external exposure in oviparous species.

摘要

多环芳烃(PAHs)在环境中广泛存在,鸟类可能通过饮食、梳理被油污染的羽毛或在胚胎发育过程中通过蛋壳污染接触到PAHs。在本研究中,检测了在卵内暴露于细胞色素P450 1A(CYP1A)诱导剂的鸡胚中两种标记的PAHs,苯并[a]芘([3H]BaP)和7,12-二甲基苯并[a]蒽([3H]DMBA)的组织分布和细胞特异性结合情况。胶带切片放射自显影片显示胆汁、肝脏、肾脏、心脏和软脑膜中有高浓度的放射性。溶剂萃取组织切片的光学显微镜放射自显影显示,在脑、心脏、肺和胸肌的某些血管中的内皮细胞中有高度选择性的结合。在绒毛尿囊膜(CAM)(一种衬于蛋壳的胚外组织)的血管内皮细胞中也观察到了结合。在体外暴露的CAM中证实了内皮结合,这意味着组织结合代谢产物是原位形成的。CYP1A抑制剂玫瑰树碱消除了CAM中靶内皮细胞的出血。因此得出结论,鸟类各种组织中的血管内皮细胞可以对环境污染物进行生物活化,并成为其毒性作用的靶点。鉴于CAM在蛋壳下方的关键位置,它可能是卵生动物外部暴露后毒物的重要靶点。

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