Metabolism of the carcinogen chromate by cellular constituents

Connett, Paul; Wetterhahn, Karen E.

doi:10.1007/bfb0111319

Cited by 287 publications

(161 citation statements)

References 92 publications

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“…The reaction of chromate with DNA creates a number of putative lesions in cellular systems including inter-and intrastrand cross-linked adducts, DNA-protein cross-links, DNA strand breaks, abasic sites, and oxidized nucleic acid bases (3)(4)(5)(6)(7). The tetrahedral anionic conformation of the +6 oxidation state of chromium facilitates active transport into cell systems through the phosphate and sulfate cellular transport systems (8). However, Cr(VI) is not the oxidation state that reacts with DNA, and cellular reduction of Cr(VI) to its stable +3 oxidation state forms a wide variety of intermediate high-valent (+4 and +5) oxidation states of chromium, as well as reductant-specific carbon-, oxygen-, and sulfurbased free radicals (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2‘-deoxyguanosine

Slade

Hailer

Martin

et al. 2005

Chem. Res. Toxicol.

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7,8-dihydro-8-oxoguanine (8-oxoG) is thought to be a major lesion formed in DNA by oxidative attack at the nucleobase guanine. Recent studies have shown that 8-oxoG has a lower reduction potential than the parent guanine and is a hot spot for further oxidation. Spiroiminodihydantoin (Sp) has been identified as one of these further oxidation products. Chromium(VI) is a human carcinogen that, when reduced by a cellular reductant such as ascorbate, can oxidize DNA. In this study, duplex DNA was reacted with Cr(VI) and ascorbate to identify and quantify the base lesions formed. Guanine bases were observed to be preferentially oxidized with 5′ guanines within purine repeats showing enhanced oxidation. Trapping of the guanine lesions by the base excision repair enzymes hOGG1 and mNEIL2 showed nearly exclusive trapping by mNEIL2, suggesting that 8-oxoG was not the major lesion but rather a lesion recognized by mNEIL2 such as Sp. Formation of the Sp lesion in the Cr(VI)/Asc oxidation reaction with DNA was confirmed by LC-ESI-MS detection. HPLC-ECD was used to identify and quantify any 8-oxoG arising from Cr(VI)/Asc oxidation of DNA. Concentrations of Cr(VI) (3.1-50 μM) with a corresponding 1:10 ratio of Asc oxidized between 0.3% and 1.5% of all guanines within the duplex DNA strand to Sp. 8-oxoG was also identified but with the highest Cr (VI) concentration converting ~0.1% of all guanines to 8-oxoG. These results show that Sp was present in concentrations ~20 times greater than that of 8-oxoG in this system. The results indicate that 8-oxoG, while present, was not the major product of Cr(VI)/Asc oxidation of DNA and that Sp predominates under these conditions. These results further imply that Sp may be the lesion that accounts for the carcinogenicity of this metal in cellular systems.

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Section: Introductionmentioning

confidence: 99%

Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2‘-deoxyguanosine

Slade

Hailer

Martin

et al. 2005

Chem. Res. Toxicol.

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“…We Another condition for ROS production would be that the Cr(V) ligands possess some degree of lability, but it is generally recognized that both Cr(VI) and Cr(V) complexes are subject to ligand exchange reactions (14,15), thus permitting the redox couple Cr(VI)/Cr(V) to act as a catalyst.…”

Section: Resultsmentioning

confidence: 99%

Reactive Oxygen Species Produced from Chromate Pigments and Ascorbate

Lefèbvre¹,

Pézerat²

1994

Environmental Health Perspectives

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The reactions of various chromate pigments and ascorbate were investigated by an ESR spin trapping technique. Production of Cr(V) was detected directly and productions of very electrophilic reactive oxygen species (ROS) was detected via the oxidation of formate. We demonstrated previously that both dissolved oxygen and Cr (V) were essential in the production of ROS in this system, and that ROS production was inhibited by catalase. We studied here the effect of solubility of different chromate pigments: sodium, calcium, strontium, basic zinc, basic lead supported on silica, and lead and barium chromates on the production of ROS in buffered medium and cell culture medium (Dublecco's Modified Eagle medium + fetal calf serum). Sodium, calcium, basic zinc, and basic lead chromates were active in the production of ROS in presence of cell culture medium, whereas lead and barium chromates were inactive. -Environ Health Perspect 1 02(Suppl 3): 243-245 (1994).

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“…The redox active site of CLIC1 is occupied by GSH. Glutathione is not only found in relatively high concentrations in the cellular milieu (0.8-8.0mM), 13 its concentration is 10-1000 times higher than other biological thiols that react faster with Cr(VI). 13 It has been hypothesized that hexavalent Cr enters the cell and reacts with GSH in the CLIC within the cellular membrane, forming Cr(IV) and some Cr(V).…”

Section: Introductionmentioning

confidence: 99%

“…Glutathione is not only found in relatively high concentrations in the cellular milieu (0.8-8.0mM), 13 its concentration is 10-1000 times higher than other biological thiols that react faster with Cr(VI). 13 It has been hypothesized that hexavalent Cr enters the cell and reacts with GSH in the CLIC within the cellular membrane, forming Cr(IV) and some Cr(V). Biological evidence also points towards Cr(IV) instead of Cr(V) being the true carcinogen as Cr(V) but not Cr(IV), triggers cellular defense mechanisms including cell death and DNA repair processes 12 .…”

Section: Introductionmentioning

confidence: 99%

Magnetic Characterization of Hypervalent Chromium Intermediates in the Reduction of Chromium(VI) by Glutathione in Acidic Solutions

Marin¹,

Koleśnik²

2017

Preprint

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Chromium (VI) is carcinogenic through intermediates formed in the cellular milieu by reduction with small reductants like glutathione (GSH), ascorbate (As), cysteine (Cys) and NADPH. Although the reduction of chromate by thiols have been investigated, the participation of Cr(IV) intermediates has been inferred only indirectly due to its refractive behavior towards EPR spectroscopy and the lack of true chromium (IV) complexes for comparative studies. Biological data from numerous reports indicate that Cr(IV) is the species most likely responsible for the carcinogenicity of Cr(VI). Our kinetic studies suggested that in acidic solutions the reduction of chromate with GSH affords mostly a chromium(IV) intermediate. As a step towards the full characterization of the paramagnetic species involved in the reduction of chromate by thiols at neutral pH, we embarked in the investigation of this reaction using the Superconducting QUantum Interference Device (SQUID) Magnetic Property Measuring System®. Our results indicate a strong influence of the temperature. At 2K, the saturation magnetization method was applied to the frozen reaction when it reached the peak of formation of intermediates. Contrary to our expectations, the contributions were calculated to be 30 % of Cr(IV) and 69 % of Cr(V) at this pH. When the Curie-Weiss method was utilized, the effective magnetic moment was dependent on the portion of the data utilized and generally higher proportion of Cr(IV) was found when the fitting is performed with data from higher temperature.

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Metabolism of the carcinogen chromate by cellular constituents

Cited by 287 publications

References 92 publications

Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2‘-deoxyguanosine

Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2‘-deoxyguanosine

Reactive Oxygen Species Produced from Chromate Pigments and Ascorbate

Magnetic Characterization of Hypervalent Chromium Intermediates in the Reduction of Chromium(VI) by Glutathione in Acidic Solutions

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