Abstract
DNA repair is critical for genotoxic susceptibility and cancer development. Forty-seven patients with head and neck squamous cell carcinoma (HNSCC) and 38 healthy controls were enrolled in this study. Among the patients, 16 subjects had metastasis of HNSCC. The extent of DNA damage, including oxidative lesions, and efficiency of repair after genotoxic treatment with hydrogen peroxide were examined using the alkaline comet assay. HNSCC cells were sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by hydrogen peroxide were repaired less effectively in cancer cells from patients with metastasis than in cells from healthy controls. We suggest that impaired DNA repair might play a role in genotoxic susceptibility of patients with head and neck cancer. Finally, as a consequence of this finding we have shown that treatment with DNA-reactive drugs could be considered as an effective therapy strategy for head and neck cancer.
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References
Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet 2004;38:445–76. doi:10.1146/annurev.genet.38.072902.092448.
Berwick M, Vineis P. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 2000;92:874–97. doi:10.1093/jnci/92.11.874.
Bohr VA. DNA damage and its processing: relation to human disease. J Inherit Metab Dis 2002;25:215–22. doi:10.1023/A:1015681929316.
Caldecott KW. Mammalian DNA single-strand break repair: an X-ra(y)ted affair. Bioessays 2001;23:447–55. doi:10.1002/bies.1063.
Collins AR, Duthie SJ, Dobson VL. Direct enzymatic detection of endogenous base damage in human lymphocyte DNA. Carcinogenesis 1993;14:1733–1735
el-Deiry WS. Role of oncogenes in resistance and killing by cancer therapeutic agents. Curr Opin Oncol. 1997;9:79–87.
Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001;411:366–74. doi:10.1038/35077232.
Iwakawa M, Goto M, Noda S, Sagara M, Yamada S, Yamamoto N, et al. DNA repair capacity measured by high throughput alkaline comet assays in EBV-transformed cell lines and peripheral blood cells from cancer patients and healthy volunteers. Mutat Res 2005;588:1–6.
Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 2001;27:247–54. doi:10.1038/85798.
Klaude M, Eriksson S, Nygren J, Ahnstrom G. The comet assay: mechanisms and technical considerations. Mutat Res 1996;363:89–96.
Koskinen WJ. Prognostic markers in head and neck carcinoma. Helsinki: Academic Dissertation Haartman Institute; 2006.
Lawrance JAL, Mais KL, Slevin NJ. Radiologically inserted gastrostomies: their use in patients with cancer of the upper aerodigestive tract. Clin Oncol (R Coll Radiol) 2003;15:87–91.
Lindahl T. Keynote: past, present, and future aspects of base excision repair. Prog Nucleic Acid Res Mol Biol 2001;68:17–30.
Lindahl T, Wood RD. Quality control by DNA repair. Science 1999;286:1897–905. doi:10.1126/science.286.5446.1897.
Mohrenweiser HW, Wilson DM III, Jones IM. Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res 2003;526:93–125. doi:10.1016/S0027-5107(03)00049-6.
Parshad R, Sanford KK. Radiation-induced chromatid breaks and deficient DNA repair in cancer predisposition. Crit Rev Oncol Hematol 2001;37:87–96. doi:10.1016/S1040-8428(00)00111-6.
Saha DT, Davidson BJ, Wang A, Pollock AJ, Orden RA, Goldman R. Quantification of DNA repair capacity in whole blood of patients with head and neck cancer and healthy donors by comet assay. Mutat Res 2008;650(1):55–62. Jan 31.
Schmezer P, Rajaee-Behbahani N, Risch A, Thiel S, Rittgen W, Drings P, et al. Rapid screening assay for mutagen sensitivity and DNA repair capacity in human peripheral blood lymphocytes. Mutagenesis 2001;16:25–30. doi:10.1093/mutage/16.1.25.
Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184–91. doi:10.1016/0014-4827(88)90265-0.
Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med 2004;10:789–99. doi:10.1038/nm1087.
Wu X, Gu J, Spitz MR. Mutagen sensitivity: a genetic predisposition factor for cancer. Cancer Res 2007;67:3493–5. doi:10.1158/0008-5472.CAN-06-4137.
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This work was supported by grant N301 099 32/3581 from Polish Ministry of Science and Higher Education.
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Rusin, P., Olszewski, J., Morawiec-Bajda, A. et al. Role of impaired DNA repair in genotoxic susceptibility of patients with head and neck cancer. Cell Biol Toxicol 25, 489–497 (2009). https://doi.org/10.1007/s10565-008-9103-9
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DOI: https://doi.org/10.1007/s10565-008-9103-9