Comparative microarray analysis of basal gene expression in mouse Hepa-1c1c7 wild-type and mutant cell lines.

Comparative microarray analysis of basal gene expression in mouse Hepa-1c1c7 wild-type and mutant cell lines.
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小鼠 Hepa-1c1c7 野生型和突变细胞系基础基因表达的比较微阵列分析。

DOI:
10.1093/toxsci/kfi194
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发表时间:
2005
期刊:
Toxicological sciences : an official journal of the Society of Toxicology.
影响因子:
--
通讯作者:
Zacharewski,TR
Zacharewski,TR
中科院分区:
--
文献类型:
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作者:
Fong,CJ;Burgoon,LD;Zacharewski,TR

文献摘要

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Hepa-1c 1c 7野生型和苯并[a]芘抗性衍生的突变细胞系已被用于阐明涉及芳烃受体(AhR)的途径和机制。然而,很少有人关注其他生物过程,这些生物过程可能在孤立的细胞系之间存在差异。在这项研究中,小鼠cDNA微阵列代表4858个基因被用来研究小鼠Hepa-1c 1c 7野生型和c1(截短Cyp 1a 1蛋白),c4(AhR核转位,ARNT,缺陷)和c12(低AhR水平)突变细胞系之间的基础基因表达的差异。令人惊讶的是,与野生型细胞相比,c1突变体表现出最大数量的基因表达变化,其次分别是c4和c12系。基础基因表达的差异与细胞系在形态、线粒体活性和增殖率方面的特异性变化一致。MTT和直接细胞计数分析表明,c4和c12突变体表现出增加的增殖活性相比,野生型细胞,而c1突变体表现出降低的活性。本研究进一步表征了Hepa-1c 1c 7野生型和突变型细胞,并确定了在与这些细胞系进行比较机制研究时应考虑的生物学过程的显著差异。
Hepa-1c1c7 wild-type and benzo[a]pyrene-resistant derived mutant cell lines have been used to elucidate pathways and mechanisms involving the aryl hydrocarbon receptor (AhR). However, there has been little focus on other biological processes which may differ between the isolated lines. In this study, mouse cDNA microarrays representing 4858 genes were used to examine differences in basal gene expression between mouse Hepa-1c1c7 wild-type and c1 (truncated Cyp1a1 protein), c4 (AhR nuclear translocator, ARNT, deficient), and c12 (low AhR levels) mutant cell lines. Surprisingly, c1 mutants exhibited the greatest number of gene expression changes compared to wild-type cells, followed by c4 and c12 lines, respectively. Differences in basal gene expression were consistent with cell line specific variations in morphology, mitochondrial activity, and proliferation rate. MTT and direct cell count assays indicate both c4 and c12 mutants exhibit increased proliferative activity when compared to wild-type cells, while the c1 mutants exhibited decreased activity. This study further characterizes Hepa-1c1c7 wild-type and mutant cells and identifies significant differences in biological processes that should be considered when conducting comparative mechanistic studies with these lines.