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暴露于苯并[a]芘的亚马逊鱼类巨脂鲤(Colossoma macropomum,居维叶,1818年)中的Ras癌基因和缺氧诱导因子-1α(hif-1α)表达

Ras oncogene and Hypoxia-inducible factor-1 alpha (hif-1α) expression in the Amazon fish Colossoma macropomum (Cuvier, 1818) exposed to benzo[a]pyrene.

作者信息

Silva Grazyelle Sebrenski da, Fé Luciana Mara Lopes, Silva Maria de Nazaré Paula da, Val Vera Maria Fonseca de Almeida E

机构信息

Laboratory of Ecophysiology and Molecular Evolution (LEEM), Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, AM, Brazil.

Department of Morphology of the Institute of Biological Sciences (DM-ICB) Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil.

出版信息

Genet Mol Biol. 2017 Apr-Jun;40(2):491-501. doi: 10.1590/1678-4685-GMB-2016-0066. Epub 2017 May 8.

DOI:10.1590/1678-4685-GMB-2016-0066
PMID:28486571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5488454/
Abstract

Benzo[a]pyrene (B[a]P) is a petroleum derivative capable of inducing cancer in human and animals. In this work, under laboratory conditions, we analyzed the responses of Colossoma macropomum to B[a]P acute exposure through intraperitoneal injection of four different B[a]P concentrations (4, 8, 16 and 32 μmol/kg) or corn oil (control group). We analyzed expression of the ras oncogene and the Hypoxia-inducible factor-1 alpha (hif-1α) gene using quantitative real-time PCR. Additionally, liver histopathological changes and genotoxic effects were evaluated through the comet assay. Ras oncogene was overexpressed in fish exposed to 4, 8 of 16 μmol/kg B[a]P, showing 4.96, 7.10 and 6.78-fold increases, respectively. Overexpression also occurred in hif-1α in fish injected with 4 and 8 μmol/kg B[a]P, showing 8.82 and 4.64-fold increases, respectively. Histopathological damage in fish liver was classified as irreparable in fish exposed to 8, 16 and 32 μmol/kg μM B[a]P. The genotoxic damage increased in fish injected with 8 and 16 μmol/kg in comparison with the control group. Acute exposure of B[a]P was capable to interrupt the expression of ras oncogene and hif-1α, and increase DNA breaks due to tissue damage.

摘要

苯并[a]芘(B[a]P)是一种能够在人类和动物体内诱发癌症的石油衍生物。在本研究中,我们在实验室条件下,通过腹腔注射四种不同浓度(4、8、16和32 μmol/kg)的B[a]P或玉米油(对照组),分析了巨脂鲤对B[a]P急性暴露的反应。我们使用定量实时PCR分析了ras癌基因和缺氧诱导因子-1α(hif-1α)基因的表达。此外,通过彗星试验评估了肝脏组织病理学变化和遗传毒性效应。在暴露于4、8或16 μmol/kg B[a]P的鱼类中,ras癌基因过度表达,分别增加了4.96、7.10和6.78倍。在注射了4和8 μmol/kg B[a]P的鱼类中,hif-1α也出现了过度表达,分别增加了8.82和4.64倍。在暴露于8、16和32 μmol/kg B[a]P的鱼类中,肝脏组织病理学损伤被归类为无法修复。与对照组相比,注射8和16 μmol/kg的鱼类遗传毒性损伤增加。B[a]P的急性暴露能够中断ras癌基因和hif-1α的表达,并由于组织损伤增加DNA断裂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/65f6cb374f56/1415-4757-gmb-1678-4685-GMB-2016-0066-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/3fa078f4c8e2/1415-4757-gmb-1678-4685-GMB-2016-0066-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/9b36ef478832/1415-4757-gmb-1678-4685-GMB-2016-0066-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/9c0fad00075e/1415-4757-gmb-1678-4685-GMB-2016-0066-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/d470260fb1cf/1415-4757-gmb-1678-4685-GMB-2016-0066-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/65f6cb374f56/1415-4757-gmb-1678-4685-GMB-2016-0066-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/3fa078f4c8e2/1415-4757-gmb-1678-4685-GMB-2016-0066-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/9b36ef478832/1415-4757-gmb-1678-4685-GMB-2016-0066-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/9c0fad00075e/1415-4757-gmb-1678-4685-GMB-2016-0066-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/d470260fb1cf/1415-4757-gmb-1678-4685-GMB-2016-0066-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ca/5488454/65f6cb374f56/1415-4757-gmb-1678-4685-GMB-2016-0066-gf05.jpg

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