Mutagenic spectrum resulting from DNA damage by oxygen radicals.

Oxygen free radicals are highly reactive species that damage DNA and cause mutations. We determined the mutagenic spectrum of oxygen free radicals produced by the aerobic incubation of single-stranded M13mp2 DNA with Fe2+. The Fe2(+)-treated DNA was transfected into component Escherichia coli, and mutants within the nonessential lac Z alpha gene for beta-galactosidase were identified by decreased alpha-complementation. The frequency of mutants obtained with 10 microM Fe2+ was 20- to 80-fold greater than that obtained with untreated DNA. Mutagenesis was greater after the host cells were exposed to UV irradiation to induce the SOS "error-prone" response. The ability of catalase, mannitol, and superoxide dismutase to diminish mutagenesis indicates the involvement of oxygen free radicals. The sequence data on 94 of the mutants establish that mutagenesis results primarily from an increase in single-base substitutions. Ninety-four percent of the mutants with detectable changes in nucleotide sequence were single-base substitutions, the most frequent being G----C transversions, followed by C----T transitions and G----T transversions. The clustering of mutations at distinct gene positions suggests that Fe2+/oxygen damage to DNA is nonrandom. This mutational spectrum provides evidence that a multiplicity of DNA lesions produced by oxygen free radicals in vitro are promutagenic and could be a source of spontaneous mutations.

[1]  O. Aruoma,et al.  Damage to the bases in DNA induced by hydrogen peroxide and ferric ion chelates. , 1989, The Journal of biological chemistry.

[2]  H. Rosen,et al.  Oxygen-based free radical generation by ferrous ions and deferoxamine. , 1989, The Journal of biological chemistry.

[3]  M. Meuth,et al.  DNA sequence determination of γ-radiation-induced mutations of the hamster aprt locus , 1989 .

[4]  O. Aruoma,et al.  Iron ion-dependent modification of bases in DNA by the superoxide radical-generating system hypoxanthine/xanthine oxidase. , 1989, The Journal of biological chemistry.

[5]  J. Cadet,et al.  UV-induced pyrimidine hydrates in DNA are repaired by bacterial and mammalian DNA glycosylase activities. , 1989, Biochemistry.

[6]  P. Taylor,et al.  Body iron stores and the risk of cancer. , 1988, The New England journal of medicine.

[7]  H. Loman,et al.  60Co γ-rays induce predominantly C/G to G/C transversions in double-stranded M13 DNA , 1988 .

[8]  J. Cadet,et al.  The repairability of oxidative free radical mediated damage to DNA: a review. , 1988, International journal of radiation biology.

[9]  S. Linn,et al.  DNA damage and oxygen radical toxicity. , 1988, Science.

[10]  L. Loeb,et al.  Mutagenesis by the autoxidation of iron with isolated DNA. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[11]  T. Steitz,et al.  Genetic and crystallographic studies of the 3',5'-exonucleolytic site of DNA polymerase I. , 1988, Science.

[12]  K. Tindall,et al.  Changes in DNA base sequence induced by gamma-ray mutagenesis of lambda phage and prophage. , 1988, Genetics.

[13]  S. Kawanishi,et al.  Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide. , 1987, Cancer research.

[14]  J. Piette,et al.  Singlet oxygen‐induced mutations in M13 lacZ phage DNA. , 1987, The EMBO journal.

[15]  H. Kasai,et al.  Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues , 1987, Nature.

[16]  L. Recio,et al.  Evidence for reactive oxygen species inducing mutations in mammalian cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Touati,et al.  Oxygen-dependent mutagenesis in Escherichia coli lacking superoxide dismutase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[18]  H. Ayaki,et al.  Specificity of ionizing radiation-induced mutagenesis in the lac region of single-stranded phage M13 mp10 DNA. , 1986, Nucleic acids research.

[19]  R. Floyd,et al.  Formation of 8-hydroxydeoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promoter, tetradecanoylphorbolacetate. , 1986, Biochemical and biophysical research communications.

[20]  I. Fridovich.  Biological effects of the superoxide radical. , 1986, Archives of biochemistry and biophysics.

[21]  R. Stevens,et al.  Iron-binding proteins and risk of cancer in Taiwan. , 1986, Journal of the National Cancer Institute.

[22]  T. Kunkel,et al.  The base substitution fidelity of eucaryotic DNA polymerases. Mispairing frequencies, site preferences, insertion preferences, and base substitution by dislocation. , 1986, The Journal of biological chemistry.

[23]  S. Wallace,et al.  Exonuclease III recognizes urea residues in oxidized DNA. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[24]  T. Kunkel,et al.  The mutational specificity of DNA polymerase-beta during in vitro DNA synthesis. Production of frameshift, base substitution, and deletion mutations. , 1985, The Journal of biological chemistry.

[25]  S. Lesko,et al.  Induction of 6-thioguanine-resistant mutants by hyperoxia and γ-irradiation: effect of compromising cellular antioxidant systems , 1985 .

[26]  J. Cadet,et al.  Radiation-induced decomposition of the purine bases within DNA and related model compounds. , 1985, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[27]  P. Cerutti.  Prooxidant states and tumor promotion. , 1985, Science.

[28]  J. Eaton,et al.  Hemoglobin. A biologic fenton reagent. , 1984, The Journal of biological chemistry.

[29]  J. E. Leclerc,et al.  Sequence analysis of ultraviolet-induced mutations in M13lacZ hybrid phage DNA. , 1984, Journal of molecular biology.

[30]  R. Hertzberg,et al.  Cleavage of DNA with methidiumpropyl-EDTA-iron(II): reaction conditions and product analyses. , 1984, Biochemistry.

[31]  T. Kunkel.  Mutational specificity of depurination. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Nishimura,et al.  Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. , 1984, Nucleic acids research.

[33]  R. Meneghini,et al.  Cell killing and DNA damage by hydrogen peroxide are mediated by intracellular iron. , 1984, The Biochemical journal.

[34]  R. Aft,et al.  Hemin-mediated DNA strand scission. , 1983, The Journal of biological chemistry.

[35]  B. Ames,et al.  Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. , 1983, Science.

[36]  D. Sagher,et al.  Insertion of nucleotides opposite apurinic/apyrimidinic sites in deoxyribonucleic acid during in vitro synthesis: uniqueness of adenine nucleotides. , 1983, Biochemistry.

[37]  S. Linn,et al.  Purification and characterization of an apurinic/apyrimidinic endonuclease from HeLa cells. , 1981, The Journal of biological chemistry.

[38]  R. Schaaper,et al.  Depurination causes mutations in SOS-induced cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Bart Barrell,et al.  The nucleotide sequence of bacteriophage φX174 , 1978 .

[40]  L. Mosulishvili,et al.  Content of some trace elements in sarcoma M-1 DNA in dynamics of malignant growth. , 1974, Cancer research.

[41]  T. Lindahl,et al.  Rate of depurination of native deoxyribonucleic acid. , 1972, Biochemistry.

[42]  S. Greer,et al.  Studies on depurination of DNA by heat. , 1962, Journal of molecular biology.

[43]  P. D. de Jong,et al.  Base substitutions, frameshifts, and small deletions constitute ionizing radiation-induced point mutations in mammalian cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[44]  B. Chance,et al.  Reactive oxygen intermediates in biochemistry. , 1986, Annual review of biochemistry.

[45]  L. Loeb,et al.  Mutagenesis by apurinic/apyrimidinic sites. , 1986, Annual review of genetics.

[46]  I. Fridovich.  Superoxide dismutases: regularities and irregularities. , 1983, Harvey lectures.

[47]  T. Kunkel,et al.  Infidelity of DNA synthesis associated with bypass of apurinic sites. , 1983, Proceedings of the National Academy of Sciences of the United States of America.