title: Delineation of the chemical pathways underlying nitric oxide-induced homologous recombination in mammalian cells.
abstract: Inflammation is an important risk factor for cancer. During inflammation, macrophages secrete nitric oxide (NO*), which reacts with superoxide or oxygen to create ONOO- or N2O3, respectively. Although homologous recombination causes DNA sequence rearrangements that promote cancer, little was known about the ability of ONOO- and N2O3 to induce recombination in mammalian cells. Here, we show that ONOO- is a potent inducer of homologous recombination at an integrated direct repeat substrate, whereas N2O3 is relatively weakly recombinogenic. Furthermore, on a per lesion basis, ONOO(-)-induced oxidative base lesions and single-strand breaks are significantly more recombinogenic than N2O3-induced base deamination products, which did not induce detectable recombination between plasmids. Similar results were observed in mammalian cells from two different species. These results suggest that ONOO(-)-induced recombination may be an important mechanism underlying inflammation-induced cancer.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Tanyel
authors.initials: T
authors.lastname: Kiziltepe
authors.forename: Amy
authors.initials: A
authors.lastname: Yan
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Vidya S
authors.initials: VS
authors.lastname: Jonnalagadda
authors.forename: Peter C
authors.initials: PC
authors.lastname: Dedon
authors.forename: Bevin P
authors.initials: BP
authors.lastname: Engelward
mesh_terms: D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D004247:DNA / Q000235:genetics; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D010957:Plasmids; D011995:Recombination, Genetic / Q000187:drug effects* / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D004247:DNA