title: Can the L5178Y Tk+/- mouse lymphoma assay detect epigenetic silencing?
abstract: The mouse lymphoma L5178Y Tk(+/-) assay is broadly used in toxicology to assess genotoxicity because of its known sensitivity to genotoxicants that act through a variety of mechanisms, which may include epigenetic DNA methylation. This brief article highlights the studies that have contributed to this conjecture and suggests an addition to the experimental design that could identify if the test substance is a potential epimutagen acting via hypermethylation.
authors.affiliation: US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, Division of Food Contact Notification, College Park, MD 20740, USA.
authors.forename: Tsu-Fan
authors.initials: TF
authors.lastname: Cheng
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Patton
authors.forename: Kristi
authors.initials: K
authors.lastname: Muldoon-Jacobs
mesh_terms: D000630:Aminopterin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D019175:DNA Methylation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D063185:Epigenetic Repression / Q000187:drug effects*; D005069:Evaluation Studies as Topic; D019271:Hypoxanthine / Q000378:metabolism; D007940:Leukemia L5178 / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014271:Trifluridine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D009153:Mutagens; D009363:Neoplasm Proteins; D019271:Hypoxanthine; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D000630:Aminopterin; D014271:Trifluridine; D013936:Thymidine
keywords: DNA methylation; Epigenetics; Genetic toxicology; Mouse Lymphoma Assay; TK L5178Y