title: Profiles of gene expression changes in L5178Y mouse lymphoma cells treated with methyl methanesulfonate and sodium chloride.
abstract: 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.
authors.affiliation: Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA. sseidel2@dow.com
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Seidel
authors.forename: Barney R
authors.initials: BR
authors.lastname: Sparrow
authors.forename: H Lynn
authors.initials: HL
authors.lastname: Kan
authors.forename: William T
authors.initials: WT
authors.lastname: Stott
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Schisler
authors.forename: V Ann
authors.initials: VA
authors.lastname: Linscombe
authors.forename: B Bhaskar
authors.initials: BB
authors.lastname: Gollapudi
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy*; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D051379:Mice; D009153:Mutagens / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009153:Mutagens; D012965:Sodium Chloride; D008741:Methyl Methanesulfonate