Metal-induced lethality and mutagenesis: Possible role of apurinic intermediates

Schaaper, Roel M.; Koplitz, R. Marlene; Tkeshelashvili, L.K.; Loeb, Lawrence A.

doi:10.1016/0027-5107(87)90001-7

Cited by 51 publications

(34 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such crosslinks are expected to stop DNA replication (28,29) and may correlate with the toxicity of CrCl3 in the mutagenesis assay with E. coli. The toxicity of Crtt' in the present study was similar to that reported by Schaaper et al (23). Since DNA-protein crosslinking is also mediated by Crtt' in vitro (26) it might be involved in the inhibition of DNA replication observed at higher concentrations of chromium (20).…”

Section: Resultssupporting

confidence: 78%

“…However, due to the poor ability of Cr"' ions to cross the cell membrane in vivo, these studies have generally proven negative. In contrast, DNA replication in vitro using synthetic polynucleotides and/or OX174 DNA templates in the presence of CrCl3 or CrCl2 (which rapidly becomes Cr"' in aqueous solution) shows a chromium-dependent increase in the frequency of nucleotide misincorporation (15,16,23 In our preliminary experiments (20), the effects of CrCl3 on DNA replication in vitro were examined in the presence of both template-bound Cr"' and free Cr"' ions. Under these conditions, low concentrations of Cr"' increased, then decreased, DNA polymerase activity and also promoted increased polymerase processivity (20).…”

Section: Resultsmentioning

confidence: 99%

“…Both Cr"' and Crvy have been surprisingly refractory in producing mutagenic DNA damage in vitro (16,23 (25,26) but may also be mutagenic directly or by indirect interference with DNA replication fidelity and bypass of DNA lesions. Many different experimental approaches have been used to determine the mutagenic mechanism of Cr"' compounds.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

A Possible Role for Chromium(III) in Genotoxicity

Snow¹

1991

Environmental Health Perspectives

View full text Add to dashboard Cite

Chromium is found in the environment in two major forms: reduced Cil' and CrVy, or chromate.Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable Cr"I species. Cr'l, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular Crl" can react slowly with both nucleic acids and proteins and can be genotoxic. We have investigated the genotoxicity of Cr"P in vitro using a DNA replication assay and in vivo by CaCl2-mediated transfection of chromium-treated DNA into Escherichia coli. When DNA replication was measured on a Cr"'-treated template using purified DNA polymerases (either bacterial or mammalian), both the rate of DNA replication and the amount of incorporation per polymerase binding event (processivity) were greatly increased relative to controls. When transfected into E. coli, Cr"l-treated M13mp2 bacteriophage DNA showed a dose-dependent increase in mutation frequency. These results suggest that Cr"' alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that Cr"' can contribute to chromiummediated carcinogenesis.

show abstract

Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A Possible Role for Chromium(III) in Genotoxicity

Snow¹

1991

Environmental Health Perspectives

View full text Add to dashboard Cite

show abstract

“…Since transversions involving deoxyadenosine substitution in SOS-induced cells are characteristic of mutagenesis via depurination (25), it seemed reasonable that the mutagenesis by oxygen free radicals might proceed by this pathway. Depurination of DNA has been shown to be enhanced by exposure of DNA to Cu2 +, Cr3+, and Ni2 + (42), and apurinic sites have been shown to be a product of radiation damage to DNA (39), a closely related process. However, our inability to abolish mutagenesis by incubation of Fe2 +-treated DNA with an apurinic endonuclease or with alkali argues strongly against requirement of an apurinic site or a closely related lesion for mutagenesis.…”

Section: Resultsmentioning

confidence: 99%

Mutagenesis by the autoxidation of iron with isolated DNA.

Loeb

James

Waltersdorph

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

137

View full text Add to dashboard Cite

Oxygen free radicals are highly reactive species generated by many cellular oxidation-reduction processes. These radicals damage cellular constituents and have been causally implicated in the pathogenesis of many human diseases. We report here that oxygen free radicals generated by Fe2+ in aqueous solution are mutagenic. Aerobic incubation of 4X174 am3 (amber 3 mutation) DNA with Fe2+ results in decreased phage survival when the treated DNA is transfected into Escherichia coli spheroplasts. Transfection of the treated DNA into SOS-induced spheroplasts results in an increase in mutagenesis as great as 50-fold. Both killing and mutagenesis can be prevented by binding of Fe2+ with deferoxamine or by the addition of catalase or mannitol. These results suggest that DNA damage and mutagenesis brought about by Fe2+ are likely to occur by a Fenton-type mechanism that involves the generation of (i) hydrogen peroxide by the autoxidation of iron and (ii) hydroxyl radicals by the interaction of the hydrogen peroxide with Fe2+. DNA sequence analysis of the Fe2+-induced mutants indicates that reversion of the phage phenotype to wild type occurs largely by a transversion type of mutation involving substitution of deoxyadenosine for thymidine opposite a template deoxyadenosine. Mutagenesis is not abolished by incubation of Fe22+-treated 4X174 am3 DNA with an apurinic endonuclease and only partially abolished by incubation with alkali, suggesting that a large fraction of the mutagenesis by oxygen free radicals is not caused by formation of apurinic sites but instead involves an as-yet-to-be-defined alteration in deoxyadenosine. These fmdings raise the possibility that free iron localized in cellular DNA may cause mutations by the generation of oxygen free radicals.A portion of the total cellular oxygen metabolism proceeds by a sequence of one-electron reductions that result in oxygen free-radical intermediates. Processes reported to yield oxygen free radicals include phagocytosis, ischemic cell injury, and drug toxicity (1-4). The resultant free radicals have been hypothesized to be causative factors in aging (5), carcinogenesis (5, 6), and radiation injury (7) and to be a contributory factor in tumor promotion (8)(9)(10) with the overall reaction being the iron-catalyzed interaction between 02 and H202 to form OH-or a similarly reactive species (Haber-Weiss reaction):

show abstract

“…Many studies demonstrated that nickel ions may cause infidelity of DNA replication in various ways (73,74). The findings included altered substrate conformation at the substrate-binding site of DNA polymerase, altered enzyme conformation at the catalytic site of DNA polymerase, and changed template-base specificity (73).…”

Section: Infidelity Of Dna Synthesis and Inhibition Of Dna Repairmentioning

confidence: 99%

Risk assessment of nickel carcinogenicity and occupational lung cancer.

Shen

Zhang

1994

Environ Health Perspect

View full text Add to dashboard Cite

Recent progress in risk assessment of nickel carcinogenicity and its correlation with occupational lung cancer in nickelexposed workers is reviewed. Epidemiological investigations provide reliable data indicating the close relation between nickel exposure and high lung cancer risk, especially in nickel refieries. The nickel species-specific effects and the doseresponse relationship between nickel exposure and lung cancer are among the main questions that are explored extensively. It is also suggested that some confounding factors such as cigarette smoking cannot be neglected. The determination of nickel concentration in lung tissue may be conducive to estimating the nickel exposure level, but it is uncertain whether the high nickel content in lung tissue indicates high lung cancer risk in nickel-exposed workers. Immunologic studies suggest that the suppressive effect ofnickel on NK cell activity and interferon production may also be involved in the mechanisms of nickel carcinogenesis. As a potential mutagen, nickel can cause chromosome damage both in vitro and in vivo; and on a molecular basis, nickel is found to induce DNA damage (DNA strandbreaks and crosslinks, infidelity of DNA replication, inhibition ofDNA repair, and the helical transition ofB-DNA toZ-DNA) by binding ofnickel ions to DNA and nuclear proteins. The discovery of oncogene promises both a challenge and an opportunity for nickel carcinogenesis research. It can be predicted that, with the rapid development ofmolecular biology and oncology, new approaches will be established for both understanding and controlling nickel-induced occupational lung cancer.

show abstract

Metal-induced lethality and mutagenesis: Possible role of apurinic intermediates

Cited by 51 publications

References 29 publications

A Possible Role for Chromium(III) in Genotoxicity

A Possible Role for Chromium(III) in Genotoxicity

Mutagenesis by the autoxidation of iron with isolated DNA.

Risk assessment of nickel carcinogenicity and occupational lung cancer.

Contact Info

Product

Resources

About