Reaction of chromium(VI) with hydrogen peroxide in the presence of glutathione: Reactive intermediates and resulting DNA damage

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00018a016· OSTI ID:5109387

Aiyar, J; Berkovits, H J; Wetterhahn, K E ^[1]; Floyd, R A ^[2]

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1. Dartmouth Coll., Hanover NH (United States)
2. Oklahoma Medical Research Foundation, Oklahoma City (United States)

The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromium(V)-glutathione complexes and the glutathione thiyl radical. Incubation of chromium(VI) with glutathione prior to addition of hydrogen peroxide led to formation of peroxochromium(V) species and a dramatic increase in hydroxyl radical production over that detected in the reaction of chromium(VI) with hydrogen peroxide alone. In contrast, addition of chromium(VI) to a preincubated mixture of glutathione and hydrogen peroxide led to a decrease in hydroxyl radical production over that obtained in the reaction of chromium(VI) with hydrogen peroxide. When pBR322 DNA was added to the above reactions, the extent of chromium(VI)-induced DNA strand breakage correlated with the relative amount of hydroxyl radical formed. Reaction of chromium(VI) with calf thymus DNA in the presence of a preincubated mixture of glutathione and hydrogen peroxide led to detection of the 8-hydroxydeoxyguanosine adduct, whose formation correlated with that of hydroxyl radical production. No significant chromium-DNA adduct formation was detected. The results suggest that, in the cellular metabolism of chromium(VI), performed chromium(V)-glutathione complexes may react with hydrogen peroxide in a Fenton-type manner to produce hydroxyl radical as the DNA-damaging agent. However, if glutathione reacts with hydrogen peroxide prior to exposure to chromium(VI), the amount of hydroxyl radical generated may not be sufficient to cause significant DNA damage. Thus, the metabolic pathway of chromium(VI) reduction is important in determining the nature and extent of chromium(VI)-induced DNA damage.

• OSTI ID: 5109387
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 3:6; ISSN 0893-228X; ISSN CRTOE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION SPECTROSCOPY
ADDUCTS
ANIMALS
BIOSYNTHESIS
BODY
CARCINOGENS
CATTLE
CHEMICAL REACTIONS
CHROMIUM
COMPLEXES
COWS
DNA
DNA ADDUCTS
DOMESTIC ANIMALS
DRUGS
ELECTRON SPIN RESONANCE
ELECTROPHORESIS
ELEMENTS
ENZYME ACTIVITY
GLUTATHIONE
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
HYDROXYL RADICALS
IN VITRO
ION EXCHANGE MATERIALS
LYMPHATIC SYSTEM
MAGNETIC RESONANCE
MAMMALS
MATERIALS
METABOLISM
METALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADICALS
RADIOPROTECTIVE SUBSTANCES
REACTION INTERMEDIATES
REDUCTION
RESONANCE
RUMINANTS
SPECTRA
SPECTROSCOPY
STRAND BREAKS
SYNTHESIS
THYMUS
TOXICITY
TRANSITION ELEMENTS
ULTRAVIOLET SPECTRA
VERTEBRATES