Advertisement

The Mer Phenotype: Human Tumor Cell Strains Defective in Repair of Alkylation Damage

  • Daniel B. Yarosh
  • Michael R. Mattern
  • Dominic A. Scudiero
  • Rufus S. DayIII

Abstract

The integrity of DNA is vitally important to cellular function and a wide variety of organisms possess repair mechanisms to preserve DNA structure and its faithful replication. Much of our understanding of human DNA repair comes from the study of xeroderma pigmentosum (XP). Patients with this disease show sun sensitivity and a high incidence of skin cancer among their symptoms [for review see 1,2]. XP is inherited in a Mendelian fashion and cells from many tissues of XP patients show hypersensitivity to UV, suggesting that a germ line mutation is responsible for the disease. In addition to cellular hypersensitivity, XP cells are deficient in support of growth of UV-irradiated SV40, herpes simplex virus and and adenovirus3,4,5. XP cells grown in culture fail to remove UV-induced pyrimidine dimers from their DNA while normal cells do6. UV-irradiated XP cells have been permeabilized and supplied with exogenous endonucleases which incise UV-irradiated DNA, whereupon dimers were excised and cellular hypersensitivity was reduced78. These data suggest that in XP a germ line mutation results in inactivation of excision repair of pyrimdine dimers throughout the body and the persistence of high levels of pyrimidine dimers in epidermal DNA leads to oncogenic transformation.

Keywords

Germ Line Mutation Xeroderma Pigmentosum Pyrimidine Dimer Alkylation Damage MNNG Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kraemer, K. (1980) Clinical Derm. 4: 1–33.Google Scholar
  2. 2.
    Cleaver, J.E. and D. Bootsma (1975) Ann. Rev. Genet. 9: 19–38.PubMedCrossRefGoogle Scholar
  3. 3.
    Aaronson, S.A. and C.D. Lytle (1970) Nature 228: 359–361.PubMedCrossRefGoogle Scholar
  4. 4.
    Lytle, C.D., S.A. Aaronson and E. Harvey (1972) Intl. J. Rad. Biol. 22: 159–165.Google Scholar
  5. 5.
    Day, R.S. III (1974) Photochem. Photobiol. 19: 9–13.PubMedCrossRefGoogle Scholar
  6. 6.
    Setlow, R.B., J.D. Regan and J. German (1969) Proc. Natl. Acad. Sci. ( USA ) 64: 1035–1039.PubMedCrossRefGoogle Scholar
  7. 7.
    Tanaka, K., H. Hayakawa, M. Sekiguchi and Y. Okada (1977) Proc. Natl. Acad. Sci. ( USA ) 74: 2958–2962.PubMedCrossRefGoogle Scholar
  8. 8.
    Tanaka, K., M. Sekiguchi and Y. Okada (1975) Proc. Natl. Acad. Sci. ( USA ) 72: 4071–4075.PubMedCrossRefGoogle Scholar
  9. 9.
    Day, R.S. III, C.H.J. Ziolkowski, D.A. Scudiero, S.A. Meyer and M.R. Mattern (1980) in “Genetic and Environmental Factors in Experimental and Human Cancer” H.V. Gelboin et al. eds. Japan Sci. Soc. Press, Tokyo, pp 247–257.Google Scholar
  10. 10.
    Day, R.S. III, C.H.J. Ziolkowski, D.A. Scudiero, S.A. Meyer and M.R. Mattern (1980) Carcinogenesis 1: 21–32.PubMedCrossRefGoogle Scholar
  11. 11.
    Day, R.S. III and C.H.J. Ziolkowski (1981) Carcinogenesis 2:213218.Google Scholar
  12. 12.
    Day, R.S. III, C.H.J. Ziolkowski, D.A. Scudiero, S.A. Meyer, A.S. Lubiniecki, A.J. Girardi, S.M. Galloway and G.D. Bynum (1980) Nature 288: 724–727.PubMedCrossRefGoogle Scholar
  13. 13.
    Day, R.S. III and C.H.J. Ziolkowski (1979) Nature 279: 797–799.PubMedCrossRefGoogle Scholar
  14. 14.
    Erickson, L.C., G. Laurent, N.A. Sharkey and K.W. Kohn (1980) Nature 288: 727–729.PubMedCrossRefGoogle Scholar
  15. 15.
    Singer, B. and T.P. Brent (1981) Proc. Natl. Acad. Sci. ( USA ) 78: 856–860.PubMedCrossRefGoogle Scholar
  16. 16.
    Olsson, M. and T. Lindahl (1980) J. Biol. Chem. 255: 10569–10571.PubMedGoogle Scholar
  17. 17.
    Bogden, J.M., A. Eastman and E. Bresnick (1981) Nucleic Acids Res. 9: 3089–3103.PubMedCrossRefGoogle Scholar
  18. 18.
    Scudiero, D.A., E. Henderson, A. Norin and B. Strauss (1975) Mut. Res. 29: 473–488.CrossRefGoogle Scholar
  19. 19.
    Setlow, R.B. and J.D. Regan (1981) in “Techniques in DNA Repair-A Handbook” E.C. Friedberg and P.C. Hanawalt eds., Marcel Dekker, Inc. N.Y. pp 307–318.Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Daniel B. Yarosh
    • 1
  • Michael R. Mattern
    • 1
  • Dominic A. Scudiero
    • 2
  • Rufus S. DayIII
    • 1
  1. 1.Nucleic Acids Section, Laboratory of Molecular CarcinogenesisCIP, DCCP, NCI, NIHBethesdaUSA
  2. 2.Chemical Carcinogenesis ProgramFrederick Cancer Research CenterFrederickUSA

Personalised recommendations