Bestimmung der DNA-Schädigung in vitro

E. Dikomey

doi:10.1055/s-0038-1626526

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 2010; 49(S 01): S64-S68
DOI: 10.1055/s-0038-1626526

Übersichtsarbeit

Schattauer GmbH

Determination of DNA damage in vitro

Artikel in mehreren Sprachen: deutsch | English

Autor*innen

E. Dikomey

¹Labor für Strahlenbiologie & Experimentelle Radioonkologie, Universitäres Cancer Center Hamburg, Universitätsklinikum Hamburg-Eppendorf

Abstract

Summary

Ionising irradiation acts primarily via induction of DNA damage, among which doublestrand breaks are the most important lesions. These lesions may lead to lethal chromosome aberrations, which are the main reason for cell inactivation. Double-strand breaks can be repaired by several different mechanisms. The regulation of these mechanisms appears be fairly different for normal and tumour cells. Among different cell lines capacity of doublestrand break repair varies by only few percents and is known to be determined mostly by genetic factors. Knowledge about doublestrand break repair mechanisms and their regulation is important for the optimal application of ionising irradiation in medicine.

Keywords

DNA double-strand breaks - cell inactivation - chromosome aberration - apoptosis - G1 arrest - DNA repair - non-homologous endjoining - homologous recombination

Volltext

Referenzen

Literatur
1 Austin CM, Bellini M. The dynamic landscape of the cell nucleus. Mol Reprod Dev 2010; 77: 19-28.
2 Bentley J, Diggle CP, Harnden P. et al. DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining. Nucleic Acids Res 2004; 32: 5249-5259.
3 Borgmann K, Dede M, Wrona A. et al. For X-irradiated normal human fibroblasts, only half of cell inactivation results from chromosomal damage. International journal of radiation oncology, biology, physics 2004; 58: 445-452.
4 Borgmann K, Haeberle D, Doerk T. et al. Genetic determination of chromosomal radiosensitivities in G0-and G2-phase human lymphocytes. Radiother Oncol 2007; 83: 196-202.
5 Borgmann K, Hoeller U, Nowack S. et al. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. Int J Radiat Oncol Biol Physics 2008; 71: 256-264.
6 Borgmann K, Raabe A, Reuther S, et al. The potential role of G2-but not of G0-radiosensitivity for predisposition of prostate cancer. Radiother Oncol 2010; 96: 19-24.
7 Branzei D, Foiani M. Maintaining genome stability at the replication fork. Nat Rev Mol Cell Biol 2010; 11: 208-219.
8 Denecker G, Vercammen D, Declercq W, Vandenabeele P. Apoptotic and necrotic cell death induced by death domain receptors. Cell Mol Life Sci 2001; 58: 356-370.
9 Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. International J Radiat Oncol Biol Physics 1995; 33: 781-796.
10 Dikomey E, Borgmann K, Brammer I, Kasten-Pisula U. Strahlenempfindlichkeit von Tumorzellen. In: Zeller WJ, zur Hausen H. (eds) Onkologie. Landsberg: ecomed; 2002: 1-14.
11 Dikomey E, Brammer I, Johansen J. et al. Relationship between DNA double-strand breaks, cell killing, and fibrosis studied in confluent skin fibroblasts derived from breast cancer patients. Int J Radiat Oncol Biol Physics 2000; 46: 481-490.
12 El-Awady RA, Dikomey E, Dahm-Daphi J. Radiosensitivity of human tumour cells is correlated with the induction but not with the repair of DNA doublestrand breaks. Br J Cancer 2003; 89: 593-601.
13 Fei P, El-Deiry WS. P53 and radiation responses. Oncogene 2003; 22: 5774-5783.
14 Forrester HB, Vidair CA, Albright N. et al. Using computerized video time lapse for quantifying cell death of X-irradiated rat embryo cells transfected with c-myc or c-Ha-ras. Cancer Res 1999; 59: 931-939.
15 Goodarzi AA, Noon AT, Deckbar D. et al. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 2008; 31: 167-177.
16 Hartlerode AJ, Scully R. Mechanisms of doublestrand break repair in somatic mammalian cells. Biochem J 2009; 423: 157-168.
17 Hoeller U, Borgmann K, Bonacker M. et al. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol 2003; 69: 137-144.
18 Iliakis G. Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence. Radiother Oncol 2009; 92: 310-315.
19 Kass EM, Jasin M. Collaboration and competition between DNA double-strand break repair pathways. FEBS Lett 2010; 584: 3703-3708.
20 Kasten-Pisula U, Menegakis A, Brammer I. et al. The extreme radiosensitivity of the squamous cell carcinoma SKX is due to a defect in double-strand break repair. Radiother Oncol 2009; 90: 257-264.
21 Kasten-Pisula U, Tastan H, Dikomey E. Huge differences in cellular radiosensitivity due to only very small variations in double-strand break repair capacity. International journal of radiation biology 2005; 81: 409-419.
22 Kuo LJ, Yang LX. Gamma-H2AX – a novel biomarker for DNA double-strand breaks. In Vivo 2008; 22: 305-309.
23 Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 2008; 9: 759-769.
24 Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Ann Rev Biochem 2010; 79: 181-211.
25 Mansour WY, Rhein T, Dahm-Daphi J. The alternative end-joining pathway for repair of DNA double-strand breaks requires PARP1 but is not dependent upon microhomologies. Nucleic Acids Res 2010; 38: 6065-6077.
26 Mansour WY, Schumacher S, Rosskopf R. et al. Hierarchy of nonhomologous end-joining, singlestrand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res 2008; 36: 4088-4098.
27 Nakano H, Shinohara K. X-ray-induced cell death: apoptosis and necrosis. Radiat Res 1994; 140: 1-9.
28 Nunez MI, Villalobos M, Olea N. et al. Radiation-induced DNA double-strand break rejoining in human tumour cells. Br J Cancer 1995; 71: 311-316.
29 Prise KM, Pinto M, Newman HC, Michael BD. A review of studies of ionizing radiation-induced double-strand break clustering. Radiat Res 2001; 156: 572-576.
30 Robertson AB, Klungland A, Rognes T, Leiros I. DNA repair in mammalian cells: Base excision repair: the long and short of it. Cell Mol Life Sci 2009; 66: 981-993.
31 Rothkamm K, Lobrich M. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proceedings of the Nat Acad Sci USA 2003; 100: 5057-5062.
32 Shinomiya N, Kuno Y, Yamamoto F. et al. Different mechanisms between premitotic apoptosis and postmitotic apoptosis in X-irradiated U937 cells. International journal of radiation oncology, biology, physics 2000; 47: 767-777.
33 Taucher-Scholz G, Heilmann J, Kraft G. Induction and rejoining of DNA double-strand breaks in CHO cells after heavy ion irradiation. Adv Space Res 1996; 18: 83-92.
34 Wu W, Wang M, Singh SK. et al. Repair of radiation induced DNA double strand breaks by backup NHEJ is enhanced in G2. DNA Repair (Amst) 2008; 7: 329-338.