title: Detailed analysis of DNA repair and senescence marker kinetics over the life span of a human fibroblast cell line.
abstract: We examined phosphorylation of H2AX, a marker for DNA double-strand breaks over the life of a human fibroblast cell line. This marker was compared with a number of other cellular senescence and DNA repair endpoints. An increase in γH2AX foci number was observed after 24 hours of repair time following DNA damage over the course of fibroblast passaging. Progressive and relatively constant changes in growth retardation, doubling time, and telomere length were also observed. The fraction of cells expressing β-gal, a marker of cellular senescence, increased considerably around the 40th passage as did some other cell morphology endpoints. The detectable γH2AX foci at 24 hours after ionizing radiation were far fewer than the number detected at 1 hour across all passage numbers. We conclude that although residual DNA damage level increases with passage number, it is unlikely to be the result of less efficient DNA repair in the aged fibroblast since most DNA damage is repaired, even at late passages.
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nuremberg, Universitätsstraße 27, D-91054 Erlangen, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Endt
authors.forename: Carl N
authors.initials: CN
authors.lastname: Sprung
authors.forename: Ulrike
authors.initials: U
authors.lastname: Keller
authors.forename: Udo
authors.initials: U
authors.lastname: Gaipl
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Luitpold V
authors.initials: LV
authors.lastname: Distel
mesh_terms: D016922:Cellular Senescence; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011839:Radiation, Ionizing; D016615:Telomere / Q000378:metabolism / Q000528:radiation effects
chemical_list: C468783:H2AX protein, human; D006657:Histones