Relationship between DNA adduct levels, repair enzyme, and apoptosis as a function of DNA methylation by azoxymethane. Academic Article uri icon


  • DNA alkylating agent exposure results in the formation of a number of DNA adducts, with O6-methyl-deoxyguanosine (O6-medG) being the major mutagenic and cytotoxic DNA lesion. Critical to the prevention of colon cancer is the removal of O6-medG DNA adducts, either through repair, for example, by O6-alkylguanine-DNA alkyltransferase (ATase) or targeted apoptosis. We report how rat colonocytes respond to administration of azoxymethane (a well-characterized experimental colon carcinogen and DNA-methylating agent) in terms of O6-medG DNA adduct formation and adduct removal by ATase and apoptosis. Our results are: (a) DNA damage is greater in actively proliferating cells than in the differentiated cell compartment; (b) expression of the DNA repair enzyme ATase was not targeted to the proliferating cells or stem cells but rather is confined primarily to the upper portion of the crypt; (c) apoptosis is primarily targeted to the stem cell and proliferative compartments; and (d) the increase in DNA repair enzyme expression over time in the bottom one-third of the crypt corresponds with the decrease in apoptosis in this same crypt region.

published proceedings

  • Cell Growth Differ

author list (cited authors)

  • Hong, M. Y., Chapkin, R. S., Wild, C. P., Morris, J. S., Wang, N., Carroll, R. J., Turner, N. D., & Lupton, J. R.

citation count

  • 41

complete list of authors

  • Hong, MY||Chapkin, RS||Wild, CP||Morris, JS||Wang, N||Carroll, RJ||Turner, ND||Lupton, JR

publication date

  • November 1999