Open AccessMutagenesis by metal-induced oxygen radicals.
Author(s) -
T. M. S. Reid,
Daniel I. Feig,
Lawrence A. Loeb
Publication year - 1994
Publication title -
environmental health perspectives
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.257
H-Index - 282
eISSN - 1552-9924
pISSN - 0091-6765
DOI - 10.1289/ehp.94102s357
Subject(s) - mutagenesis , reactive oxygen species , dna damage , carcinogenesis , mutation , microbiology and biotechnology , chemistry , dna , biochemistry , dna polymerase , polymerase , mutation frequency , radical , biology , gene
To assess the contribution of reactive oxygen species (ROS) to metal-induced mutagenesis, we have determined the spectrum of mutations in the lacZ alpha 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-alpha and -beta 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.