Modification of chromium(VI)-induced DNA damage by glutathione and cytochromes P-450 in chicken embryo hepatocytes.

Cupo, Doreen Y.; Wetterhahn, Karen E.

doi:10.1073/pnas.82.20.6755

Cited by 94 publications

(52 citation statements)

References 27 publications

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“…[3]) manganese(I1) has a slight catalytic effect on the reaction, but when that ratio equals 7 the effect of that ion is inhibitory instead, and the inhibition observed is more intense as the reductantloxidant ratio increases. Actually, manganese(I1) ion is known to be an inhibitor for many chromium(V1) redox reactions, due to its ability to act as a trapping agent for the intermediate chromium (1V) (17); however, the maximum decrease in the reaction rate that can be expected from this effect is 50% (9), and for a reductantloxidant ratio > 34 we have observed that the inhibitory effect of manganese(I1) ion on the chromium(VI)/~~-PA reaction exceeds that limit (and it would be probably larger at higher values of the reductantloxidant ratio).…”

Section: Mechanism In the Presence Of Manganese(i1) Ionmentioning

confidence: 99%

“…More recently, some interest has arisen on the kinetics and mechanism of this and similar reactions at physiological pH, since it seems probable that the mutagenic effects of the well-known carcinogen chromium(V1) require its previous reduction inside the cell, and glutathione and other biological thiols seem to b e likely candidates as reductants (2,3).…”

Section: Introductionmentioning

confidence: 99%

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Oxidation of DL-penicillamine by chromium(VI). Kinetics of formation of the thioester intermediate

Perez‐Benito¹,

Lamrhari²,

Arias³

1994

Can. J. Chem.

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, 1637 (1994). The kinetics of formation of the thioester involved as an intermediate in the reaction between chromium(V1) and or.-penicillamine in aqueous media (pH = 1-8) containing different buffers (acetate, citrate, and phosphate) has been studied by monitoring the disappearance of chromium(V1) at 370 nm and application of the initial-rates method. The initial rate is directly proportional to the initial concentrations of both oxidant and reductant, and the rate vs. pH plots show bell-shaped profiles. The reaction is catalyzed by the buffer present in the medium, the catalytic power of each buffer increasing in the order acetate < citrate < phosphate. This is explained in terms of a mechanism involving the formation of a complex between the acidic form of the buffer and HCr04-previous to the formation of the thioester. Potassium chloride and sodium sulfate do not seem to have important specific effects on the reaction rate, their effect being that of an acceleration of the reaction as the ionic strength increases. On the contrary, the sulfates of magnesium, manganese(II), and zinc (the latter only in the presence of acetate buffer) have specific effects, indicating the probable formation of several complexes. The spectrophotometric detection of the thioester at 430 nm has allowed to confirm some of the conclusions extracted from the measurement of initial rates, and suggests that this intermediate might approach a steady-state behavior in the three buffers at pH > 6.25, and also that a bimolecular reaction with DL-penicillamine might be involved in its destruction. JOAQUIN F. PEREZ-BENITO, DRISS LAMRHARI et CONCHITA ARIAS. Can. J. Chem. 72, 1637 (1994).En examinant la vitesse de disparition du chrome(V1) B 370 nm et en appliquant la mCthode des vitesses initiales, on a CtudiC la cinitique de formation du thioester impliquC comme intermkdiaire dans la rCaction du chrome(V1) et la DLpinicillamine, en milieu aqueux (pH = 1 B 8) contenant divers tampons (acCtate, citrate et phosphate). La vitesse initiale est directement proportionnelle aux concentrations B la fois de I'oxydant et du rCducteur et les courbes des vitesses en fonction du pH prksentent des profils en forme de cloche. La rCaction est catalysCe par le tampon prCsent dans le milieu, le pouvoir catalytique de chacun des tampons augmentant dans l'ordre acCtate < citrate < phosphate. On peut expliquer ces rCsultats en fonction d'un mCcanisme impliquant la formation, avant la formation du thioester, d'un complexe entre la forme acide du tampon et le HCr04-. Le chlorure de potassium et le sulfate de sodium ne semblent pas avoir d'effets spCcifiques importants sur la vitesse de la reaction; leur effet se limite B une accClCration de la rCaction lorsque la force ionique augmente. Au contraire, les sulfates de magnCsium, de manganbse(I1) et de zinc (dans ce dernier cas, uniquement en prCsence du tampon acCtate) posskdent des effets spCcifiques, suggCrant la formation probable de plusieurs complexes. La dCtection spectrophotomCtrique du thioester 2 430 nm a p...

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Section: Mechanism In the Presence Of Manganese(i1) Ionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidation of DL-penicillamine by chromium(VI). Kinetics of formation of the thioester intermediate

Perez‐Benito¹,

Lamrhari²,

Arias³

1994

Can. J. Chem.

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“…For instance, Cr(V) complexes have been reported to induce DNA breakage and %hydroxy-2'-deoxyguanosine in vitro as well as mutation in bacterial systems, and recent in vitro studies indicated that not only Cr(VI)/(V) but also the Cr(III)/ (II) redox couple serve as cyclical electron donors, in a Fenton-like reaction, to produce active oxygen species [5-81. Among the biological reductants, GSH has been reported to be present normally in millimolar concentrations in intact cells, and the modification of cellular GSH in cultured cells has been shown to alter the levels of DNA damage caused by Cr(VI) [9]. Furthermore, ESR studies have shown that Cr(II1) and Cr(V) complexes are formed during reduction of Cr(V1) by GSH in vitro, and *Corresponding author.…”

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confidence: 99%

Effect of glutathione depletion on formation of paramagnetic chromium in Chinese hamster V‐79 cells

Sugiyama

Tsuzuki

1994

FEBS Letters

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Incubation of Chinese hamster V-79 cells with either buthionine sulfoximine @SO) or diethylmaleate @EM) prior to exposure to Na&rQ resulted in a depletion of GSH. ESR study shows that the depletion of GSH by BSO caused an increase in the cellular level of Cr(V) intermediate without affecting the level of Cr(III) complex, whereas the levels of Cr(V) and (III) were both suppressed by the depletion of GSH by DEM. GSH depletion by DEM decreased cellular uptake of chromate more than that by BSO. Glutathione reductase activity in cells, which is capable of reducing Cr(VI), was una.tkcted by BSO, however a strong inhibition was observed in cells treated with DEM, indicating that DEM affects not only GSH levels but also Cr(VI)-reducing enxyme activity. Thus, the depletion of GSH in cells increases Cr(V) formation, based upon the effect of BSO. The role of intracellular GSH in Cr(V1) reduction is discussed. Key work Glutathione;Chromium; ESR; Chinese hamster V-79 cell IntroduetlonCr(V1) compounds are well known to be human carcinogens [l]. They have been shown to produce DNA single strand breaks and DNA-protein crosslinks and to inhibit the activity of enzymes such as glutathione reductase (GR) in mammalian cells [24]. In contrast to Cr(III), Cr(V1) actively enters cells by the sulfate anion transport system and is then believed to be reduced through reactive intermediates such as Cr(V) and (IV) to more stable Cr(II1) by cellular reductants including glutathione (GSH), ascorbic acid, riboflavin and flavoenzymes including GR [24]. Thus, the generation of paramagnetic chromium may play an important role in the cellular damage caused by Cr(V1). For instance, Cr(V) complexes have been reported to induce DNA breakage and %hydroxy-2'-deoxyguanosine in vitro as well as mutation in bacterial systems, and recent in vitro studies indicated that not only Cr(VI)/(V) but also the Cr(III)/ (II) redox couple serve as cyclical electron donors, in a Fenton-like reaction, to produce active oxygen species [5-81. Among the biological reductants, GSH has been reported to be present normally in millimolar concentrations in intact cells, and the modification of cellular GSH in cultured cells has been shown to alter the levels of DNA damage caused by Cr(VI) [9]. Furthermore, ESR studies have shown that Cr(II1) and Cr(V) complexes are formed during reduction of Cr(V1) by GSH in vitro, and *Corresponding author. Fax: (81) (942) 31 4377. the formation of Cr(V) in rat thymocytes and human red blood cells treated with Cr(VI) has been reported to be suppressed by thiol-reactive agents such as diethylmaleate (DEM) and N-ethylmaleimide, respectively [lO,l 11. However, none of these thiol depletors are specific for GSH alone, and the influence of GSH depletion by an agent such as buthionine sulfoximine (BSO) which can deplete the cellular store of GSH via competitive inhibition of y glutamylcysteine synthetase [12], on the formation of paramagnetic chromium in intact cells has not been investigated.In the present study, the effect of GSH depleti...

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“…However, it is not clear why these vitamins have an ability to change the chromium(V) but not the chromium(III) complex in cells. With respect to DNA damage, DNA breaks induced by chromate have been reported to be associated with cellular levels of glutathione and the activity of cytochrome P-450 reductase, whereas protein crosslinks were not dependent upon these factors (12). Furthermore, our previous studies have shown that in three different cell lines of human, mouse, and hamster origin, the order of sensitivity to DNA-protein crosslinks was not consistent with the sensitivity to formation of DNA breaks by chromate (8), suggesting that chromium-induced DNA-protein crosslinks may be formed by a different mechanism than that for single-strand breaks.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the cellular metabolism of chromium(VI) may play a role in the induction of chromate toxicity and carcinogenicity. Chromium(VI) compounds have been shown to produce DNA single-strand breaks and DNA-protein crosslinks (3,(6)(7)(8)(9)(10)(11)(12) and to selectively inhibit the activity of glutathione reductase (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Effects of vitamins on chromium(VI)-induced damage.

Sugiyama

1991

Environ Health Perspect

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The effects of vitamin E and vitamin B2 on DNA damage and cellular reduction of chromium(VI) were investigated using Chinese hamster V-79 cells. Pretreatment with a-tocopherol succinate (vitamin E) resulted in a decrease of DNA single-strand breaks produced by Na2CrO4, while similar treatment with riboflavin (vitamin B2) enhanced levels of DNA breaks. In contrast, levels of DNA-protein crosslinks induced by Na2CrO4 were unaffected by these vitamins. Electron spin resonance (ESR) studies showed that incubation of cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complexes, and cellular pretreatment with vitamin E reduced the level of the chromium(V) complex, whereas pretreatment with vitamin B2 enhanced the level of this intermediate. However, the levels of chromium(III) were unchanged by these vitamins. The uptake of chromate was not affected by vitamin E or vitamin B2, nor were the levels of glutathione or glutathione reductase activity, which are both capable of reducing chromate. ESR studies demonstrated that a chromium(V) species was formed by the reaction of Na2CrO4 with vitamin B2 and that vitamin B2 enhanced the formation of hydroxyl radicals during the reaction of Na2CrO4 and hydrogen peroxide. Treatment of cells with Na2CrO4 resulted in a decrease of glutathione reductase activity, and pretreatment with vitamin E restored the enzyme activity suppressed by this metal. However, pretreatment with vitamin B% enhanced the inhibition of this enzyme by Na2CrO4. Using a colony-forming assay, pretreatment with vitamin E dramatically decreased the cytotoxicity of Na2CrO4, while pretreatment with vitamin B2 was found to result in only a decrease of cell lethality of this metal. These results indicate that vitamin E and vitamin B2 are capable of altering the biological effects of carcinogenic chromium(VI) compounds, possibly through their abilities to modify levels of chromium (V) in cells. The results also suggest that chromate-induced cytotoxicity may not be directly correlated with the genotoxic effects of this metal. The importance of the role of vitamins in chromate-induced toxicity is discussed.

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Modification of chromium(VI)-induced DNA damage by glutathione and cytochromes P-450 in chicken embryo hepatocytes.

Cited by 94 publications

References 27 publications

Oxidation of DL-penicillamine by chromium(VI). Kinetics of formation of the thioester intermediate

Oxidation of DL-penicillamine by chromium(VI). Kinetics of formation of the thioester intermediate

Effect of glutathione depletion on formation of paramagnetic chromium in Chinese hamster V‐79 cells

Effects of vitamins on chromium(VI)-induced damage.

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