title: 3-Methyladenine DNA glycosylase-deficient Aag null mice display unexpected bone marrow alkylation resistance.
abstract: Most cells deficient in 3-methyladenine (3MeA) DNA glycosylase become sensitive to the lethal and clastogenic effects of alkylating agents. Surprisingly, myeloid progenitor bone marrow (BM) cells derived from Aag -/- mice were more resistant than those from wild-type mice to the cytotoxic effects of several alkylating agents. Moreover, an alkylation-resistant phenotype was observed in vivo using the BM micronucleus assay as a measure of chromosome damage. Flow cytometry indicated that in vivo alkylation resistance in Aag null BM cells may be restricted to cells of the myeloid lineage. These results show that in particular cell types, the initiation of base excision repair is more lethal to the cell than leaving the damaged bases unrepaired by Aag.
authors.affiliation: Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Roth
authors.forename: Leona D
authors.initials: LD
authors.lastname: Samson
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000478:Alkylation; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D019070:Cell Lineage; D045647:DNA Glycosylases; D004351:Drug Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D009699:N-Glycosyl Hydrolases / Q000172:deficiency* / Q000235:genetics
chemical_list: D000477:Alkylating Agents; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases