title: Subchronic exposure of benzo(a)pyrene interferes with the expression of Bcl-2, Ki-67, C-myc and p53, Bax, Caspase-3 in sub-regions of cerebral cortex and hippocampus.
abstract: Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous environmental contaminant. However, the mechanism of B(a)P neurotoxicity is still not clear. The aim of this study was to investigate the molecular mechanism by assay the expression of Bcl-2, C-myc, Ki-67 oncogene and p53, Bax, Caspase-3 proapoptotic gene in sub-regions of cerebral cortex and hippocampus in brain. Mice were administrated with subchronic intraperitoneal injection and oral gavage of B(a)P (2.5, 5, 10mg/kg body weight) for 13 weeks. We observed that B(a)P induced the significant increase in relative brain weights and the slight proliferation phenomenon in hippocampus in the experiment. Significant increase of C-myc, Ki-67 and p53, Bax, Caspase-3 and dramatic decrease of Bcl-2 protein levels were observed through immunohistochemical analysis. The relative higher interference of Bcl-2, C-myc, Ki-67 and p53, Bax, Caspase-3 proteins was observed in hippocampus sub-regions of dentate gyrus, cornu ammonis 3 and cornu ammonis 1. The relative lower interference of the examined genes was found in cerebral cortex sub-regions of frontal cortex, temporal cortex and parietal cortex. The results showed a region-difference manner with accompanying dose-dependent manner in brain hippocampus and cerebral cortex induced by B(a)P. These findings indicate that B(a)P-induced subchronic neural toxicity may occur through the enhancement in Bcl-2, C-myc, Ki-67 oncogenes and p53, Bax, Caspase-3 proapoptotic genes expression.
authors.affiliation: Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ji
authors.affiliation: School of Materials and Chemical Engineering, Xi'an Technological University, Xi'an 710020, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics School of Pharmacy, Fourth Military Medical University, Shaanxi 710032, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, 17Changle West Road, Shaanxi 710032, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Feng
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Huqin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Life and Geography, Qinghai Normal University, Xining 810008, China.
authors.forename: Huichun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: gaomeili@mail.xjtu.edu.cn.
authors.forename: Meilii
authors.initials: M
authors.lastname: Gao
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D053148:Caspase 3 / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics; D008813:Mice, Inbred ICR; D009687:Nuclear Proteins / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001564:Benzo(a)pyrene; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Benzo(a)pyrene; Cerebral cortex; Hippocampus; Oncogene; Proapoptotic gene