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Mutagenesis vol. 19 no. 3 pp. 195-201, May 2004
© 2004 UK Environmental Mutagen Society/Oxford University Press

Profiles of gene expression changes in L5178Y mouse lymphoma cells treated with methyl methanesulfonate and sodium chloride

Shawn D. Seidel1,3, Barney R. Sparrow2, H.Lynn Kan1, William T. Stott1, Melissa R. Schisler1, V.Ann Linscombe1 and B.Bhaskar Gollapudi1

1Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA and 2Battelle Toxicology, 505 King Avenue, Columbus, OH, USA

Treatment of cells with genotoxic chemicals is expected to set into motion a series of events including gene expression changes to cope with the damage. We have investigated gene expression changes in L5178Y TK+/– mouse lymphoma cells in culture following treatment with methyl methanesulfonate (MMS), a direct acting genotoxin, and sodium chloride (NaCl), which induces mutations in these cells through indirect mechanisms at high concentrations. The mouse lymphoma cells were treated for 4 or 24 h and the cells were harvested for RNA isolation at the end of the treatment. Analysis of the transcriptome was performed using Clontech Mouse 1.2K cDNA microarrays (1185 genes) and hybridized using 32P-labeled cDNA. The microwell methodology was used to quantify the mutagenic response. Of the genes examined, MMS altered the expression (1.5-fold or more) of only five (four at 4 h and one after 24 h treatment). NaCl altered two genes after 4 h treatment, but after 24 h it altered 19 genes (13 down- and six up-regulated). Both compounds altered the expression of several genes associated with apoptosis and NaCl altered genes involved in DNA damage/response and GTP-related proteins. This, along with other data, indicates that the widely used L5178Y TK+/–mouse lymphoma cells in culture are relatively recalcitrant in terms of modulating gene expression to deal with genotoxic insult.

3To whom correspondence should be addressed. Tel: +1 989 638 6155; Fax: +1 989 638 9305; Email: sseidel2{at}dow.com

Received on June 2, 2003; revised on December 3, 2003; accepted on March 15, 2004


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