Hydrogen peroxide cytotoxicity. Low-temperature enhancement by ascorbate or reduced lipoate

Jonas, S. K.; Riley, Patrick A.; Willson, R. L.

doi:10.1042/bj2640651

Cited by 90 publications

(32 citation statements)

References 21 publications

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“…Hydroxyl radicals are generated at sites containing reduced metal ions (Cu 1+, Fe 2+) and produce sitespecific damage. At temperatures that inhibit cellular metabolism, these ions do not undergo repeated reduction ("recycling effect"), because the reducing equivalents are not produced (Ward et al 1985;Jonas et al 1989). …”

Section: Discussionmentioning

confidence: 98%

Content of iron and copper in the nuclei and induction of pH 9-labile lesions in L5178Y sublines inversely cross-sensitive to H2O2 and x-rays

Szumiel

Kapiszewska

Kruszewski

et al. 1995

Radiat Environ Biophys

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Cells from the L5178Y murine lymphoma subline LY-R are twice as resistant to killing by ionizing radiation than the subline LY-S. In contrast, LY-R cells are more sensitive to killing by H2O2, the effect being more pronounced at 37 degrees C than 0 degree C. Initial DNA damage after H2O2 treatment (both temperatures, 5 min) has been estimated by the 'comet' assay (single-cell gel electrophoresis) and fluorescent halo technique. According to both methods, the initial damage is significantly higher in LY-R cells, particularly that inflicted at 0 degree C. Differences between DNA unwinding and rewinding abilities at pH 9 and 6.9 (estimated by the fluorescent halo technique) point to a considerable difference in pH-9-labile damage between the sublines, as observed previously for x-irradiated cells (Kapiszewska et al. 1992). In contrast to findings with x-irradiated cells, however, after H2O2 treatment this damage is more extensive in LY-R cells than in LY-S cells. Thus, the initial pH-9-labile damage corresponds to the pattern of sensitivity to H2O2 and x-rays. We suggest that this is caused by different proportions of cuprous and ferric ions found in the nuclei of LY sublines and by the different ability of these ions to react with H2O2 and water radiolysis products. The copper/iron ratio in the nucleus is 1.31 in LY-R cells and 4.84 in LY-S cells.

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Section: Discussionmentioning

confidence: 98%

Content of iron and copper in the nuclei and induction of pH 9-labile lesions in L5178Y sublines inversely cross-sensitive to H2O2 and x-rays

Szumiel

Kapiszewska

Kruszewski

et al. 1995

Radiat Environ Biophys

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“…The reason for this synergy is unknown. Chemically, it may relate to the ability of these nutrients to modify cellular oxidation-reduction status in a manner that enhances H 2 O 2 toxicity (Jonas et al, 1989) or to possible ascorbate recycling by lipoic acid in redox reactions. Biologically, the effectiveness of lipoic acid in confluent cell monolayers suggests that it may aid in killing nonproliferating SW620 HFST cells that are relatively resistant to ascorbate.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours

Casciari¹,

Riordan²,

Schmidt³

et al. 2001

Br J Cancer

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Summary Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K 3 , phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC 50 in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and nonproliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K 3 . The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing.

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“…In regard to one specific ROS, hydrogen peroxide (H202), it is well known that its addition to cell culture causes loss of viability (Rubin and Farber 1984;Schraufstatter et al 1986Schraufstatter et al , 1988Hyslop et al 1988;Kyle et al 1989;Jonas et al 1989;Cantoni et al 1989), but the exact mechanism(s) of this effect is (are) still a subject of debate.…”

Section: Introductionmentioning

confidence: 98%

Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts

1992

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The incubation of isolated hepatocytes in the presence of glucose plus glucose oxidase, a H2O2-generating system, resulted in extensive loss of cell viability, as expressed by the release of lactate dehydrogenase (LDH). Disturbance of metabolic functions such as glycogen and protein synthesis was also caused by H2O2, but in no case was malondialdehyde (MDA)-like products detected. The lytic effect of H2O2 was significantly enhanced by incubating hepatocytes in the presence of iron salts. Under these conditions, MDA-like products were detected, but lipid peroxidation and cell injury did not correlate. Iron chelators modulated the cytotoxicity of H2O2 in different (and opposite) ways: when iron was complexed with ADP, increased cell lysis was observed compared to uncomplexed iron plus H2O2. Iron-DTPA, on the contrary, decreased such a lytic effect. The preincubation of hepatocytes with desferrioxamine mesylate (Desferal; a strong iron chelator) abolished the cytolytic effects produced by the association of iron salts and H2O2, as well as the membrane oxidative injury due to H2O2 alone, thus suggesting the existence of an intracellular source of iron. This kind of mechanism (metal chelation rather than radical scavenging) is supported by the absence of any protective effect by some free radical scavengers against the oxidative injury induced by the association iron H2O2. Nevertheless, the glycogenolytic effects observed in the presence of H2O2 were not modified by Desferal. In our opinion, the cytotoxicity of the association H2O2 plus iron salts involves at least two different and independent mechanisms.

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Hydrogen peroxide cytotoxicity. Low-temperature enhancement by ascorbate or reduced lipoate

Cited by 90 publications

References 21 publications

Content of iron and copper in the nuclei and induction of pH 9-labile lesions in L5178Y sublines inversely cross-sensitive to H2O2 and x-rays

Content of iron and copper in the nuclei and induction of pH 9-labile lesions in L5178Y sublines inversely cross-sensitive to H2O2 and x-rays

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours

Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts

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