Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status

被引：47

作者：

Sprong, D ^{[1
]}

Janssen, HDL ^{[1
]}

Vens, C ^{[1
]}

Begg, AC ^{[1
]}

机构：

[1] Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands

来源：

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2006年 / 64卷 / 02期

关键词：

hypoxia; radiosensitivity; DNA repair; homologous recombination; foci;

D O I：

10.1016/j.ijrobp.2005.09.031

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: To determine the role of DNA repair in hypoxic radioresistance. Methods and Materials: Chinese hamster cell lines with mutations in homologous recombination (XRCC2, XRCC3, BRAC2, RAD51C) or nonhomologous end-joining (DNA-PKcs) genes were irradiated under normoxic (20% oxygen) and hypoxic (<0.1% oxygen) conditions, and the oxygen enhancement ratio (OER) was calculated. In addition, Fanconi anemia fibroblasts (complementation groups C and G) were compared with fibroblasts from nonsyndrome patients. RAD51 foci were studied using immunofluorescence. Results: All hamster cell tines deficient in homologous recombination showed a decrease in OER (1.5-2.0 vs. 2.6-3.0 for wild-types). In contrast, the OER for the DNA-PKcs-deficient line was comparable to wild-type controls. The two Fanconi anemia cell strains also showed a significant reduction in OER. The OER for RAD51 foci formation at late times after irradiation was considerably lower than that for survival in wild-type cells. Conclusion: Homologous recombination plays an important role in determining hypoxic cell radiosensitivity. Lower OER-s have also been reported in cells deficient in XPF and ERCC1, which, similar to homologous recombination genes, are known to play a role in cross-link repair. Because Fanconi anemia cells are also sensitive to cross-linking agents, this strengthens the notion that the capacity to repair cross-links determines hypoxic radiosensitivity. (C) 2006 Elsevier Inc.

引用

页码：562 / 572

页数：11

共 51 条

[11] Interstrand cross-links:: A new type of γ-ray damage in bromodeoxyuridine-substituted DNA [J].

Cecchini, S ;

Girouard, S ;

Huels, MA ;

Sanche, L ;

Hunting, DJ .

BIOCHEMISTRY, 2005, 44 (06) :1932-1940

[12] The Fanconi anaemia BRCA pathway [J].

D'Andrea, AD ;

Grompe, M .

NATURE REVIEWS CANCER, 2003, 3 (01) :23-34

[13]

Damia G, 1996, INT J CANCER, V66, P779, DOI 10.1002/(SICI)1097-0215(19960611)66:6<779::AID-IJC12>3.0.CO

[14]

2-Z

[15] Defects in interstrand cross-link uncoupling do not account for the extreme sensitivity of ERCC1 and XPF cells to cisplatin [J].

De Silva, IU ;

McHugh, PJ ;

Clingen, PH ;

Hartley, JA .

NUCLEIC ACIDS RESEARCH, 2002, 30 (17) :3848-3856

[16] Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells [J].

De Silva, IU ;

McHugh, PJ ;

Clingen, PH ;

Hartley, JA .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (21) :7980-7990

[17] REPAIR OF TRANS-PT(II)DIAMMINEDICHLORIDE DNA PROTEIN CROSSLINKS IN NORMAL AND EXCISION-DEFICIENT HUMAN-CELLS [J].

FORNACE, AJ ;

SERES, DS .

MUTATION RESEARCH, 1982, 94 (02) :277-284

[18] Mammalian Rad51C contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability [J].

Godthelp, BC ;

Wiegant, WW ;

van Duijn-Goedhart, A ;

Schärer, OD ;

van Buul, PPW ;

Kanaar, R ;

Zdzienicka, MZ .

NUCLEIC ACIDS RESEARCH, 2002, 30 (10) :2172-2182

[19]

HAGEN U, 1965, STRAHLENTHER ONKOL, V128, P565

[20] INTRATUMORAL PO2 PREDICTS SURVIVAL IN ADVANCED CANCER OF THE UTERINE CERVIX [J].

HOCKEL, M ;

KNOOP, C ;

SCHLENGER, K ;

VORNDRAN, B ;

BAUSSMANN, E ;

MITZE, M ;

KNAPSTEIN, PG ;

VAUPEL, P .

RADIOTHERAPY AND ONCOLOGY, 1993, 26 (01) :45-50

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