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Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair

Oncogene volume 19, pages 5034–5037 (2000)Cite this article

Abstract

DNA damages caused by cellular metabolites and environmental agents induce mutations, that may predispose to cancer. Nucleotide excision repair (NER) is a major cellular defence mechanism acting on a variety of DNA lesions. Here, we show that spontaneous mutant frequencies at the Hprt gene increased 30-fold in T-lymphocytes of 1 year old Xpc−/− mice, possessing only functional transcription-coupled repair (TCR). Hprt mutant frequencies in Xpa−/− and Csb−/− mice that both have a defect in this NER subpathway, remained low during ageing. In contrast to current models, the elevated mutation rate in Xpc−/− mice does not lead to an increased tumour incidence or premature ageing.

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References

  • Ananthaswamy HN, Ouhtit A, Evans RL, Gorny A, Kashkina P, Sands AT and Conti CJ. . 1999 Oncogene 18: 7395–7398.

  • Berg RJW, Rebel HG, Van der Horst GTJ, Mullenders LHF, Van Vloten WA and De Gruijl FR. . 2000 Cancer Res. in press.

  • Bohr VA, Smith CA, Okumoto DS and Hanawalt PC. . 1985 Cell 40: 359–369.

  • Cheo DL, Meira LB, Burns DK, Reis AM, Issac T and Friedberg EC. . 2000 Cancer Res. 60: 1580–1584.

  • Cheo DL, Ruven HJT, Meira LB, Hammer RE, Burns DK, Tappe NJ, Van Zeeland AA, Mullenders LHF and Friedberg EC. . 1997 Mutat. Res-Fundam. Mol. Mech. Mut. 374: 1–9.

  • De Vries A, Dolle ME, Broekhof JL, Muller JJ, Kroese ED, Van Kreijl CF, Capel PJA, Vijg J and Van Steeg H. . 1997 Carcinogenesis 18: 2327–2332.

  • De Vries A, Van Oostrom C, Th M, Hofhuis FM, Dortant PM, Berg RJW, De Gruijl FR, Wester PW, Van Kreijl CF, Capel PJA, Van Steeg H and Verbeek SJ. . 1995 Nature 377: 169–173.

  • Dumaz N, Duthu A, Ehrhart JC, Drougard C, Apella E, Anderson CW, May P, Sarasin A and Dayagrosjean L. . 1997 Mol. Carcinogen. 20: 340–347.

  • Fraga CG, Shigenaga MK, Park JW, Degan P and Ames BN. . 1990 Proc. Natl. Acad. Sci. USA 87: 4533–4537.

  • Friedberg EC, Bond JP, Burns DK, Cheo DL, Greenblatt MS, Meira LB, Nahari D and Reis AM. . 2000 Mutation Res. 459: 99–108.

  • Friedberg EC, Walker GC and Siede W. . 1995 DNA Repair and Mutagenesis ASM Press, Washington DC.

    Google Scholar 

  • Hoeijmakers JHJ. . 1994 Eur. J. Cancer 30A: 1912–1991.

  • Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT and Weinberg RA. . 1994 Curr. Biol. 4: 1–7.

  • Kuraoka I, Bender C, Romieu A, Cadet J, Wood RD and Lindahl T. . 2000 Proc. Natl. Acad. Sci. USA in press.

  • Le Page F, Kwoh EE, Avrutskaya A, Gentil A, Leadon SA, Sarasin A and Cooper PK. . 2000 Cell 101: 159–171.

  • Ljungman M and Zhang FF. . 1996 Oncogene 13: 823–831.

  • Mckay BC, Ljungman M and Rainbow AJ. . 1998 Oncogene 17: 545–555.

  • Mellon I, Spivak G and Hanawalt PC. . 1987 Cell 51: 241–249.

  • Odagiri Y, Uchida H, Hosokawa M, Takemoto K, Morley AA and Takeda T. . 1998 Nat. Genet. 19: 116–117.

  • Reis AM, Cheo DL, Meira LB, Greenblatt MS, Bond JP, Nahari D and Friedberg EC. . 2000 Cancer Res. 60: 1571–1579.

  • Shibutani S, Takeshita M and Grollman AP. . 1991 Nature 349: 431–434.

  • Tates AD, Van Dam FJ, De Zwart FA, Van Teylingen CMM and Natarajan AT. . 1994 Mut. Res. 309: 299–306.

  • Van der Horst GT, Van Steeg H, Berg RJ, Van Gool AJ, De Wit J, Weeda G, Morreau H, Beems RB, Van Kreijl CF, De Gruijl FR, Bootsma D and Hoeijmakers JHJ. . 1997 Cell 89: 425–435.

  • Van Oosten M, Rebel H, Friedberg EC, Van Steeg H, Van der Horst GTJ, Van Kranen HJ, Westerman A, Van Zeeland AA, Mullenders LHF, De Gruijl FR. . 2000 Proc. Natl. Acad. Sci. USA in press.

  • Wijnhoven SWP, Kool HJ, Van Oostrom C, Th M, Beems RB, Mullenders LHF, Van Zeeland AA, Van der Horst GTJ, Vrieling H and Van Steeg H. . 2000 Cancer Res. in press.

  • Wijnhoven SWP, Van Sloun PPH, Kool HJM, Weeda G, Slater R, Lohman PH, Van Zeeland AA and Vrieling H. . 1998 Proc. Natl. Acad. Sci. USA 95: 13759–13764.

  • Wood RD. . 1996 Annu. Rev. Biochem 65: 135–167.

  • Yamaizumi M and Sugano T. . 1994 Oncogene 9: 2775–2784.

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Acknowledgements

We thank C van Teijlingen for technical assistance on the isolation and culturing of splenic T-lymphocytes and selection of Hprt mutants and Dr T Jacks, MIT, for providing us with the p53+/− mice (Jacks et al., 1994). This work was financially supported by the Dutch Cancer Society (Project 96-1321).

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Authors and Affiliations

  1. Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, AL Leiden, 2333, The Netherlands

    Susan WP Wijnhoven, Leon HF Mullenders, Albert A van Zeeland & Harry Vrieling

  2. Department of Cell Biology and Genetics-MGC, Erasmus University Rotterdam, PO Box 1738, DR Rotterdam, 3000, The Netherlands

    Hanneke JM Kool & Gijsbertus TJ van der Horst

  3. JA Cohen Institute, Inter-University Institute for Radiopathology and Radiation Protection, Leiden, The Netherlands

    Leon HF Mullenders, Albert A van Zeeland & Harry Vrieling

  4. Department of Pathology, Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas, 75235-9072, Texas, TX, USA

    Errol C Friedberg

  5. Department of Carcinogenesis, National Institute of Public Health and the Environment (RIVM), Laboratory of Health Effects Research, Mutagenesis and Genetics, PO Box 1, BA Bilthoven, 3720, The Netherlands

    Harry van Steeg

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  1. Susan WP Wijnhoven
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Wijnhoven, S., Kool, H., Mullenders, L. et al. Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair. Oncogene 19, 5034–5037 (2000). https://doi.org/10.1038/sj.onc.1203844

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