Repair of alkali-labile sites within the mitochondrial DNA of RINr 38 cells after exposure to the nitrosourea streptozotocin

J Biol Chem. 1991 Feb 15;266(5):3113-7.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkylating Agents / toxicity
  • Animals
  • DNA Repair*
  • DNA, Mitochondrial / drug effects*
  • DNA, Neoplasm / isolation & purification
  • Electrophoresis, Polyacrylamide Gel
  • Rats
  • Streptozocin / toxicity*
  • Tumor Cells, Cultured


  • Alkylating Agents
  • DNA, Mitochondrial
  • DNA, Neoplasm
  • Streptozocin