title: DNA damage in cells exhibiting radiation-induced genomic instability.
abstract: Cells exhibiting radiation-induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, 50 Bell Avenue, Upton, NY 11973, USA, Laboratory of Medical and Environmental Radiobiology, Biophysical Chemistry Group, Department of Biological Sciences, CENUR del Noroeste, UdelaR, Rivera 1350, Salto 50000, Uruguay, keszenman@unorte.edu.uy.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Keszenman
authors.affiliation: 107-112 CMM/BLL, Stony Brook University, Stony Brook, NY 11794, USA and.
authors.forename: Lucia
authors.initials: L
authors.lastname: Kolodiuk
authors.affiliation: Department of Radiation Oncology, University of California, Medical Sciences I, B149, Irvine, CA 92697, USA keszenman@unorte.edu.uy.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Baulch
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans