Maier Mark S V, Legare Marie E, Hanneman William H
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523-1680, USA.
Neurotoxicology. 2007 May;28(3):594-612. doi: 10.1016/j.neuro.2007.01.002. Epub 2007 Jan 13.
Genome-wide oligonucleotide DNA microarrays and real time RT-PCR were used to assess differential gene expression in rat glioma and hepatoma cell lines after exposure to the aryl hydrocarbon receptor (AhR) agonist 3,3',4,4',5-pentachlorobiphenyl (penta-CB). Under maximal inducing concentrations for cytochrome P450 1A1 (CYP1A1) in H4IIE rat hepatoma cells, both H4IIE and C6 rat glioma cells were exposed to sub-micromolar concentrations of penta-CB for 24h. Differential gene expression for approximately 28,000 gene probes were computationally analyzed and compared. As expected, penta-CB potently activated CYP1A1/2 transcription in liver-derived H4IIE hepatoma cells yet did not do so in brain-derived C6 glioma cells. Additionally, we show that penta-CB causes: (1) distinct patterns of gene expression between tumor cells derived from liver or brain; (2) robust transcriptional activation of select C6 glioma gene ontologies; (3) over-expression of H4IIE hepatoma genes associated with tumor progression in liver; (4) greater than 100-fold over-expression of C6 glioma genes associated with protein processing and programmed cell death and/or metastasis; (5) tissue-selective histone deacetylase inhibition in C6 glioma, but not H4IIE hepatoma cells as signaled by galectin-1 over-expression.
利用全基因组寡核苷酸DNA微阵列和实时逆转录聚合酶链反应（RT-PCR），评估大鼠胶质瘤和肝癌细胞系在暴露于芳烃受体（AhR）激动剂3,3',4,4',5-五氯联苯（五氯联苯）后的基因表达差异。在H4IIE大鼠肝癌细胞中细胞色素P450 1A1（CYP1A1）的最大诱导浓度下，将H4IIE和C6大鼠胶质瘤细胞暴露于亚微摩尔浓度的五氯联苯中24小时。对约28,000个基因探针的差异基因表达进行了计算分析和比较。正如预期的那样，五氯联苯在肝源性H4IIE肝癌细胞中强烈激活CYP1A1/2转录，但在脑源性C6胶质瘤细胞中则不然。此外，我们发现五氯联苯会导致：（1）肝源性或脑源性肿瘤细胞之间不同的基因表达模式；（2）选择的C6胶质瘤基因本体的强大转录激活；（3）与肝脏肿瘤进展相关的H4IIE肝癌基因的过表达；（4）与蛋白质加工、程序性细胞死亡和/或转移相关的C6胶质瘤基因的过表达超过100倍；（5）如半乳糖凝集素-1过表达所表明的，C6胶质瘤细胞中存在组织选择性组蛋白去乙酰化酶抑制，但H4IIE肝癌细胞中没有。
