Glutathione peroxidase and catalase modulate the genotoxicity of arsenite

Wang, T.S; Shu, Yueyue; Liu, Y.C; Jan, K.Y; Huang, Hongbiao

doi:10.1016/s0300-483x(97)00071-1

Cited by 117 publications

(41 citation statements)

References 33 publications

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“…[24][25][26][27][28] For example, an H 2 O 2 -resistant Chinese hamster ovary (CHO) cell line displays crossresistance to arsenic, a catalase-deficient CHO cell line is hypersensitive to arsenic, and free radical scavengers such as DMSO can confer protection against arsenic-induced apoptosis. 29 Therefore, given the high sensitivity of APL cells to arsenic, we investigated the role of PML/RARa expression, as well as of GSH and ROS levels, as determinants of sensitivity in these and other, less sensitive AML cell lines.…”

Section: Introductionmentioning

confidence: 99%

Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines

et al. 2003

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Arsenic trioxide (As 2 O 3 ) is an effective treatment for acute promyelocytic leukemia (APL), but is less effective against other leukemias. Although the response of APL cells to As 2 O 3 has been linked to degradation of the PML/RARa fusion oncoprotein, there is evidence that PML/RARa expression is not the only mediator of arsenic sensitivity. Indeed, we found that exogenous expression of PML/RARa did not sensitize a non-APL leukemic line to As 2 O 3 . To evaluate possible other determinants of sensitivity of leukemic cells to As 2 O 3 , we derived two arsenic-resistant NB4 subclones. Despite being approximately 10-fold more resistant to arsenic than their parental cell line, PML/RARa protein was still degraded by As 2 O 3 in these cells, providing further evidence that loss of expression of the oncoprotein does not confer arsenic sensitivity. Both arsenic-resistant clones contained high glutathione (GSH) levels, however, and we found that GSH depletion coupled with As 2 O 3 treatment dramatically inhibited their growth. Annexin V-staining and TUNEL analysis confirmed a synergistic induction of apoptosis. In addition, these cells failed to accumulate ROS in response to arsenic treatment, in contrast to their arsenic-sensitive parental cells, unless cotreated with buthionine sulfoximine. While other malignant cells did not show a good correlation between arsenic sensitivity and GSH content, GSH depletion nevertheless sensitized all cell lines examined, regardless of their initial response to arsenic alone. These findings suggest that PML/RARa expression is not a determinant of arsenic sensitivity, and further support the coupling of GSH depletion and arsenic treatment as a novel treatment for human malignancies that are unresponsive to arsenic alone. Leukemia (2003) 17, 931-940.

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Section: Introductionmentioning

confidence: 99%

Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines

et al. 2003

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“…Studies have shown that its carcinogenesis may be attributed to inhibition of DNA repair by inhibiting repair enzymes of dithiol groups [2][3][4] . Recently, it has been associated with generation of reactive oxygen species [5][6][7] . A study using an earlier version of the alkaline elution method has indicated that arsenic could induce DNA strand breaks in human fetal lung fibroblasts 8) .…”

Section: Introductionmentioning

confidence: 99%

Arsenic induces DNA damage via reactive oxygen species in human cells

Morimoto

Takeshita

et al. 2001

Environ Health Prev Med

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To elucidate arsenic-induced oxidative DNA damage, the genotoxicity of arsenic in human cells was comparatively studied with single cell gel electrophoresis (SCGE) assay in combination with the observation of the protective effects of dimethyl sulfoxide (DMSO) and catalase. Arsenic, at the concentration of 2.4 mM by coincubation for 24 hours, significantly induced DNA damage in HL60, a human promyelocytic leukemia cell line. In contrast, significant DNA damage was found in human mononucleocytes at the concentration of 4.8 mM or above. The cells were incubated separately with DMSO (12 mM/l), a well-known hydroxyl radical (OH ----) scavenger, and catalase (1,300 U/ml), a hydrogen peroxide (H 2 O 2 ) scavenger, for 6 hours and then further coincubated with various concentrations of arsenic for 24 hours at 37°°°°C and 5% CO 2 . The findings showed that both DMSO and catalase significantly reduced the arsenic-induced tail moment, a parameter of total damaged DNA, in HL60 and mononucleocytes. Hence our findings indicate that arsenic, with micromolar concentrations, induces typical and various extents of DNA damage in human cells via reactive oxygen species in a dose-dependent manner.

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“…Arsenic-induced oxidative stress or redox disturbance (17,(19)(20)(21) contributes to DNA damage (22)(23)(24), chromosomal aberrations (25), and protein expression alterations (22,26). However, its role in arsenic carcinogenesis is not completely understood.…”

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confidence: 99%

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Trouba

Geisenhoffer

Germolec

2002

Environ Health Perspect

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Arsenic is a carcinogen that poses a significant health risk in humans. Based on evidence that arsenic has differential effects on human, rodent, normal, and transformed cells, these studies addressed the relative merits of using normal human epidermal keratinocytes (NHEK) and immortalized human (HaCaT) and mouse (HEL30) keratinocytes when examining stressinduced gene expression that may contribute to carcinogenesis. We hypothesize that redox-related gene expression is differentially modulated by arsenic in normal versus immortalized keratinocytes. To test the hypothesis, we exposed keratinocytes to sodium arsenite for 4 or 24 hr, at which time serine threonine kinase-25 (

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Glutathione peroxidase and catalase modulate the genotoxicity of arsenite

Cited by 117 publications

References 33 publications

Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines

Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines

Arsenic induces DNA damage via reactive oxygen species in human cells

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

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