“Excision” of Bases from DNA Methylated by Carcinogens in Vivo and Its Possible Significance in Mutagenesis and Carcinogenesis

  • P. D. Lawley
Part of the Basic Life Sciences book series


The methylating carcinogens can be classified into two broad groups according to their chemical reactivities—those typifying Ingold’s SN2 alkylating agents, such as methyl methanesulfonate and dimethyl sulfate, and those such as N-methyl-N-nitrosourea and N-methyl-N’-nitro-N-nitrosoguanidine, envisaged to methylate through the highly reactive methyldiazonium ion, often described as SN 1 agents. These differences in reaction mechanism are reflected in different ratios of methylation products formed in DNA. It should be noted that di­methylnitrosamine requires metabolic activation to yield the same methylating species as generated by hydrolysis of N-methyl-N-nitrosourea. The principal distinction of the SN 1 agents is their ability to alkylate 0-atom sites in nucleic acids, including the O-6 atom of guanine (reviewed by Lawley, 1972) and phosphodiester groups (Shooter et al., 1974).


Alkylating Agent Methane Sulfonate Dimethyl Sulfate Chemical Hydrolysis Methyl Methane Sulfonate 
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  1. Capps, M. J., O’Connor, P. J. and Craig, A. W. (1973) Biochim. Biophys. Acta, 331, 33.PubMedGoogle Scholar
  2. Cerdà-Olmedo, E., Hanawalt, P. C. and Guerola, N. (1968). J. Mol. Biol. 33, 705.PubMedCrossRefGoogle Scholar
  3. Craddock, V. M. (1973a). Nature 245, 386.PubMedCrossRefGoogle Scholar
  4. Craddock, V. M. (1973b). Biochim. Biophys. Acta 312, 202.PubMedGoogle Scholar
  5. Frei, J. V. (1971). Int. J. Cancer 7, 436.PubMedCrossRefGoogle Scholar
  6. Frei, J. V. and Lawley, P. D. (1975). Chem.-Biol. Interact. (in press).Google Scholar
  7. Kirtikar, D. M. and Goldthwait, D. A. (1974). Proc. Nat. Acad. Sci. U.S.A. 71, 2022.Google Scholar
  8. Lawley, P. D. (1972). In Topics in Chemical Carcinogenesis (Nakahara, W., Takayama, S., Sugimura, T. and Odashima, S., eds.), p. 237. University Park Press, Baltimore; and University of Tokyo Press, Tokyo.Google Scholar
  9. Lawley, P. D. (1974). Mutat. Res. 23, 283.PubMedCrossRefGoogle Scholar
  10. Lawley, P. D. and Brookes, P. (1968). Biochem. J. 109, 433.PubMedGoogle Scholar
  11. Lawley, P. D. and Orr, D. J. (1970). Chem.-Biol. Interact. 2, 154.PubMedCrossRefGoogle Scholar
  12. Loveless, A. (1969). Nature 223, 206.PubMedCrossRefGoogle Scholar
  13. Loveless, A. and Hampton, C. L. (1969). Mutat. Res. 7, 1.PubMedCrossRefGoogle Scholar
  14. Maitra, S. C. and Frei, J. V. (1975). Chem.-Biol. Interact. 10, 285.PubMedCrossRefGoogle Scholar
  15. Margison, G. P. and O’Connor, P. J. (1973). Biochim. Biophys. Acta 331, 349.PubMedGoogle Scholar
  16. O’Connor, P. J., Capps, M. J. and Craig, A. W. (1973). Brit. J. Cancer 27, 153.PubMedCrossRefGoogle Scholar
  17. Shooter, K. V., Howse, R., Shah, S. A. and Lawley, P. D. (1974). Biochem. J. 137, 303.PubMedGoogle Scholar
  18. Swann, P. F. and Magee, P. N. (1968). Biochem. J. 110, 39.PubMedGoogle Scholar
  19. Verly, W. G. (1974). Biochem. Pharmacol. 23, 3.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • P. D. Lawley
    • 1
  1. 1.Chester Beatty Research Institute Institute of Cancer ResearchRoyal Cancer HospitalLondonEngland

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