title: O6-alkylguanine DNA lesions trigger apoptosis.
abstract: It is unclear whether alkylating agents induce apoptosis because they damage DNA, or because they damage other cellular targets. Isogenic Chinese hamster ovary (CHO) cell lines varying in the repair of O6-alkylguanine (O6AlkG) were examined for their propensity to undergo alkylation-induced apoptosis. Robust O6AlkG repair virtually eliminated the apoptogenic effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU, carmustine), as did the expression of BCL-2. O6AlkG repair had no effect on apoptosis induced by tumor necrosis factor alpha or by gamma-irradiation. We conclude that alkylating agents induce apoptosis by virtue of their ability to modify DNA bases and, more specifically, that O6AlkG lesions can trigger such programmed cell death.
authors.affiliation: Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: W
authors.initials: W
authors.lastname: Meikrantz
authors.forename: M A
authors.initials: MA
authors.lastname: Bergom
authors.forename: A
authors.initials: A
authors.lastname: Memisoglu
authors.forename: L
authors.initials: L
authors.lastname: Samson
mesh_terms: D000818:Animals; D017209:Apoptosis; D016466:CHO Cells / Q000187:drug effects / Q000528:radiation effects; D002330:Carmustine / Q000494:pharmacology; D006224:Cricetinae; D005434:Flow Cytometry; D005720:Gamma Rays / Q000009:adverse effects; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D008769:Methylnitronitrosoguanidine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine