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与接触商业香烟的总颗粒物相关的抗血管生成和致畸活性。

Anti-angiogenic and teratological activities associated with exposure to total particulate matter from commercial cigarettes.

作者信息

Ejaz Sohail, Ashraf Muhammad, Nawaz Muhammad, Lim Chae Woong, Kim Bumseok

机构信息

Angiogenesis and Toxicology Research Laboratory, Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

出版信息

Food Chem Toxicol. 2009 Feb;47(2):368-76. doi: 10.1016/j.fct.2008.11.029. Epub 2008 Dec 3.

DOI:10.1016/j.fct.2008.11.029
PMID:19084571
Abstract

Angiogenesis and the embryonic movement (EM) pathway are evolutionarily conserved mechanisms, which are essential for embryonic development. Deviation in these processes from exposure to cigarette total particulate matter (TPM) may produce vascular, morphogenetic, and teratological disorders. The anti-angiogenic and teratogenic potential of TPM from commercially available cigarettes was studied. In vitro effects of TPM on angiogenesis were determined with different assays utilizing human umbilical vein endothelial cells (HUVEC). A chicken embryo model was used to demonstrate the in vivo effects of TPM on EM, vascular development, and organogenesis. The current study provides evidence that cigarette TPM plays an impeding role in endothelial cell proliferation, migration, tube formation, and sprouting, which are crucial factors in angiogenesis. Video recordings and kinematic analyses of the TPM exposed chicken embryos revealed a striking decrease in EM. Likewise, exposure of TPM to embryos resulted in ocular, mandibular, and abdominal hemorrhaging. Several teratologies including ectopia cordis, as well as bi-trunked and mammoth headed embryos were frequent findings among TPM treated embryos. These results are strongly reminiscent of morphogenetic and teratogenic deformities in TPM exposed embryos. This shows that cigarette smoking during pregnancy can be fatal to growing embryos. In addition, TPM may produce defective morphogenesis, leading to various pathologies.

摘要

血管生成和胚胎运动(EM)途径是进化上保守的机制,对胚胎发育至关重要。接触香烟总颗粒物(TPM)导致这些过程出现偏差可能会产生血管、形态发生和致畸性疾病。本研究探讨了市售香烟中TPM的抗血管生成和致畸潜力。利用人脐静脉内皮细胞(HUVEC),通过不同检测方法确定了TPM对血管生成的体外作用。使用鸡胚模型来证明TPM对胚胎运动、血管发育和器官发生的体内作用。当前研究提供了证据,表明香烟TPM在内皮细胞增殖、迁移、管形成和芽生过程中发挥阻碍作用,而这些过程是血管生成的关键因素。对暴露于TPM的鸡胚进行视频记录和运动学分析显示,胚胎运动显著减少。同样,将TPM暴露于胚胎会导致眼部、下颌和腹部出血。在经TPM处理的胚胎中,经常发现包括心异位以及双头和巨头胚胎在内的几种畸形。这些结果强烈让人联想到暴露于TPM的胚胎中的形态发生和致畸性畸形。这表明孕期吸烟可能对发育中的胚胎致命。此外,TPM可能会导致形态发生缺陷,从而引发各种病理状况。

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