Advertisement

The Enhanced Repair of O6-Alkylguanine in Mammalian Systems

  • P. J. O’Connor
  • G. P. Margison
  • R. Montesano
  • J. D. Buckley
  • Y.-H. Chu
  • D. P. Cooper
  • R. A. Smith
  • N. J. Curtin
  • K. Snell
  • J. Ashby
  • C. Bradbrook
  • J. A. Styles
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)

Abstract

The “adaptive” response in bacteria may be defined in terms of a reduction in the toxicity and mutagenicïty of certain agents by pre-exposure to low levels of the agent and the effect is intimately associated with an enhanced DNA repair process1,2,3. In mammals it is premature to conclude that an equivalent system exists since none of these parameters have been examined simultaneously but there are now a number of systems in which pretreatment with various carcinogenic agents has been shown to enhance the capacity of certain tissues to repair O6-alkylguanine lesions in DNA. These systems are outlined here and the possible relationship of this phenomenon to carcinogenicity is considered.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    L. Samson and J. Cairns, A new pathway for DNA repair in Escherischia coli. Nature (London) 267: 281 (1977).CrossRefGoogle Scholar
  2. 2.
    P.F. Schendel and P.E. Robins, Repair of O6 -methylguanine in adapted Escherischia coli. Proc.Natl.Acad.Sci.U.S.A. 75:6017 (1978) 280: 76 (1979).Google Scholar
  3. 3.
    P. Karran, T. Lindahl and B. Griffin, Adaptive response to alkylating agents involves alteration in situ of O6 -methylguanine residues in DNA. Nature (London) 280: 76 (1979).Google Scholar
  4. 4.
    R. Montesano, H. Brésil and G.P. Margison, Increased excision of O6-methylguanine from rat liver DNA after chronic administration of dimethylnitrosamine. Cancer Res. 39: 1798 (1979).PubMedGoogle Scholar
  5. 5.
    R. Montesano, H. Brésil, G. Planche-Martel, G.P. Margison and A.E. Pegg, Effect of chronic treatment of rats with dimethylnitrosamine on the removal of O6-methylguanine from DNA. Cancer Res. 40: 452 (1980).Google Scholar
  6. 6.
    P.F. Swann and R. Mace, Disappearance of O6-methylguanine from rat liver DNA during chronic dimethylnitroaamine administ6rat-ion. A possible similarity between the system removing O6-me-thylguanine from DNA in rat liver and in E.coli. Chem.-Biol. Interact. submitted for publication.Google Scholar
  7. 7.
    A.E. Pegg and J.W. Nicoll, Nitrosamine carcinogenesis: the importance of the persistence in DNA of alkylated bases in the organotropism of tumour induction, in “Screening Tests in Chemical Carcinogenesis” R. Montesano, B. Bartsch and L. Tomatis eds. IARC, Lyon, 1976, p181.Google Scholar
  8. 8.
    A.E. Pegg and G. Hui, Formation and subsequent removal of O6- methylguanine from DNA in rat liver and kidney after small doses of dimethylnitrosamine. Biochem.J. 173: 739 (1978).CrossRefGoogle Scholar
  9. 9.
    G.P. Margison, J.M. Margison and R. Montesano, Accumulation of O6-methylguanine in non-target-tissue DNA during chronic administration of dimethylnitrosamine. Biochem.J. 165: 463 (1977).CrossRefGoogle Scholar
  10. 10.
    G.P. Margison, N. Brésil, J.M. Margison and R. Montesano, Effect of chronic administration of dimethylnitrosamine on the excision of O6-methylguanine from rat liver DNA. Cancer Lett. 2: 79 (1976).CrossRefGoogle Scholar
  11. 11.
    H.K. Cooper, E. Hauenstein, G.F. Kolar and P. Kleihues, DNA alkylation and oncogenesis by 3,3-dimethyl-l-phenyltriazene, Acta Neuropathol (Berl) 43: 105 (1978).CrossRefGoogle Scholar
  12. 12.
    G.P. Margison, N.K. Curtin, K. Snell and A.W. Craig, Effect of chronic N,N-diethylnitrosamine on the excision of O6-ethylguanine from rat liver DNA. Br.J.Cancer, 40: 809 (1979).CrossRefGoogle Scholar
  13. 13.
    E. Scherer, A.P. Steward and P. Emmelot, Kinetics of formation of O -ethylguanine in, and its removal from, liver DNA of rats receiving diethylnitrosamine. Chem.-Biol.Interact. 19: 1 (1977).CrossRefGoogle Scholar
  14. 14.
    G.P. Margison, J.M. Margison and R. Montesano, Methylated purines in the DNA of various Syrian golden hamster tissues after administration of hepatocarcinogenic doses of dimethylnitrosamine. Biochem.J. 157: 627 (1976).CrossRefGoogle Scholar
  15. 15.
    G.P. Margison, J.A. Swindell, C.H. Ockey and A.W. Craig, The effect of a single dose of dìmethylnitrosamine in the Chinese hamster and persistence of DNA alkylation products in selected tissues. Carcinogenesis 1: 91 (1980).CrossRefGoogle Scholar
  16. 16.
    J.D. Buckley, P.J. O’Connor, and A.W. Craig, Pretreatment with acetylaminofluorene enhances the repair of O -methylguanine. Nature (London) 281: 403 (1979).CrossRefGoogle Scholar
  17. 17.
    P. Gupta and M.A. Sirover, Induction of base excision repair in human cells. J.Cell Biol. 83: 5a (1979).Google Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • P. J. O’Connor
  • G. P. Margison
  • R. Montesano
    • 2
  • J. D. Buckley
    • 1
    • 5
  • Y.-H. Chu
    • 1
    • 3
  • D. P. Cooper
    • 1
  • R. A. Smith
    • 1
  • N. J. Curtin
    • 4
  • K. Snell
    • 4
  • J. Ashby
    • 5
  • C. Bradbrook
    • 5
  • J. A. Styles
    • 5
  1. 1.Paterson LaboratoriesChristie Hospital and Holt Radium InstituteManchesterUK
  2. 2.Unit of Chemical CarcinogenesisInternational Agency for Research on CancerCedex 2France
  3. 3.Shanghai Cancer InstituteShanghaiChina
  4. 4.Department of BiochemistryUniversity of SurreyGuildfordUK
  5. 5.Central Toxicology LaboratoryImperial Chemical Industrïes Ltd.Macclesfield, CheshireUK

Personalised recommendations