Mutagenesis by metal-induced oxygen radicals

Academic Article

Abstract

  • To assess the contribution of reactive oxygen species (ROS) to metal-induced mutagenesis, we have determined the spectrum of mutations in the lacZα gene after exposure of M13mp2 DNA to Fe2+, Cu2+, and Ni2+. With iron and copper ions, mutations are clustered and are predominantly single-base substitutions. Fe, Cu, and phorbol ester-stimulated neutrophils also produced tandem double CC → TT mutations. This mutation may provide a marker for the role of oxidative damage in carcinogenesis. Mutagenesis by Ni2+ required the complexing of the metal to a tripeptide and the addition of H2O2. To assess the contribution of ROS in mammalian cells, we determined the spectrum of mutations produced when purified DNA polymerases-α and -β synthesized DNA using a template that had been damaged by ROS. The mutation spectra produced by the two polymerases indicates that these enzymes substitute different nucleotides opposite the same lesions.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Reid TM; Feig DI; Loeb LA
  • Start Page

  • 57
  • End Page

  • 61
  • Volume

  • 102
  • Issue

  • SUPPL. 3