title: DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer.
abstract: BACKGROUND
  Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood.
  
  
  METHODS
  Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group).
  
  
  RESULTS
  Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression.
  
  
  CONCLUSIONS
  BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species-mediated genotoxic stress in the metastatic brain.
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA. woditschkas@mail.nih.gov steegp@mail.nih.gov.
authors.forename: Stephan
authors.initials: S
authors.lastname: Woditschka
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Evans
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Renata
authors.initials: R
authors.lastname: Duchnowska
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: L Tiffany
authors.initials: LT
authors.lastname: Reed
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Diane
authors.initials: D
authors.lastname: Palmieri
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: George
authors.initials: G
authors.lastname: Sledge
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Brunilde
authors.initials: B
authors.lastname: Gril
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Mirit I
authors.initials: MI
authors.lastname: Aladjem
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Fu
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Flores
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Gökmen-Polar
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szutowicz-Zielińska
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mandat
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trojanowski
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Och
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Bogumiła
authors.initials: B
authors.lastname: Czartoryska-Arlukowicz
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.affiliation: Affiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA. woditschkas@mail.nih.gov steegp@mail.nih.gov.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Steeg
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D051135:Rad51 Recombinase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013113:Spin Labels; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; C491163:Bard1 protein, mouse; D044767:Ubiquitin-Protein Ligases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; C001803:tempol