title: Pluripotent cells display enhanced resistance to mutagenesis.
abstract: Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate. We also measured levels of key enzymes in the base excision repair (BER) pathway in each cell line before and after exposure to the mutagen. Our results confirm that pluripotent cells normally maintain lower frequencies of point mutations than differentiated cells, and show that differentiated cells exhibit a large increase in mutation frequency following a moderate mutagenic exposure, whereas pluripotent cells subjected to the same exposure show no increase in mutations. This result likely reflects the higher levels of BER proteins detectable in pluripotent cells prior to exposure and supports our thesis that maintenance of enhanced genetic integrity is a fundamental characteristic of pluripotent cells.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cooper
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States.
authors.forename: I-Chung
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Hernandez
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
authors.forename: Christi A
authors.initials: CA
authors.lastname: Walter
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States. Electronic address: john.mccarrey@utsa.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: McCarrey
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D057890:Epigenomics; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008741:Methyl Methanesulfonate
keywords: Base excision repair; DNA repair; Epigenetic programming; Stem cells