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ToxSci Advance Access originally published online on May 11, 2005
Toxicological Sciences 2005 86(2):342-353; doi:10.1093/toxsci/kfi194
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Comparative Microarray Analysis of Basal Gene Expression in Mouse Hepa-1c1c7 Wild-Type and Mutant Cell Lines

C. J. Fong*, L. D. Burgoon*,{dagger} and T. R. Zacharewski*,1

* Department of Biochemistry and Molecular Biology, National Food Safety and Toxicology Center, Center for Integrative Toxicology, and {dagger} Department of Pharmacology and Toxicology Michigan State University, East Lansing, Michigan, 48824

Received March 17, 2005; accepted May 2, 2005

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.

Key Words: benzo[a]pyrene; aryl hydrocarbon receptor; Hepa-1c1c7.


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