title: Repair of alkali-labile sites within the mitochondrial DNA of RINr 38 cells after exposure to the nitrosourea streptozotocin.
abstract: Studies were initiated to investigate whether mechanisms exist within mitochondria to repair damage incurred by mitochondrial DNA after exposure to alkylating toxins. A clonal isolate from a rat insulinoma cell line was utilized to measure the formation and repair of alkali-labile sites within the mitochondrial genome after exposure to the alkylating antibiotic streptozotocin. Alkali-labile sites were formed in mitochondrial DNA in a dose-dependent fashion. Eight hours after exposure to the toxin, 55% of the lesions were removed. The level of repair increased to 70% after 24 h. In comparison, only 46% of N7-methylguanines were removed across the entire cellular genome. These studies demonstrate that streptozotocin causes appreciable mitochondrial DNA damage in a dose-dependent manner and provide the first evidence that a repair mechanism for alkali-labile sites is present within the mitochondrion.
authors.affiliation: Department of Structural and Cellular Biology, University of South Alabama, Mobile 36688.
authors.forename: C C
authors.initials: CC
authors.lastname: Pettepher
authors.forename: S P
authors.initials: SP
authors.lastname: LeDoux
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
authors.forename: G L
authors.initials: GL
authors.lastname: Wilson
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D051381:Rats; D013311:Streptozocin / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D000477:Alkylating Agents; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D013311:Streptozocin