Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian cells

Wang, Tsu Shing; Hsu, Tsung Yang; Chung, Chiao Hui; Wang, Alexander S.S.; Bau, Da Tian; Jan, Kun Yan

doi:10.1016/s0891-5849(01)00581-0

Cited by 113 publications

(62 citation statements)

References 42 publications

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“…It is not known whether these DNA-protein cross-links are the same as those revealed by the technique of potassium-sodium dodecyl sulfate (K-SDS) precipitation (25). Although we have concluded that Fpg-digestible adducts are greater in quantity and more prevalent in different cell types than PK-digestible adducts in arsenite-treated cells, the arsenite-induced Fpg-and PK-digestible adducts were both sensitive to modulators of NO, oxidant, myeloperoxidase, and calcium in HL60 and NB4 cells (1). We therefore propose identical pathways for the induction of oxidative DNA and DNA-protein cross-links on treatment with arsenite ( Figure 2).…”

Section: Arsenite Induces Oxidized Guanine Products and Dna-protein Ccontrasting

confidence: 56%

“…Under our experimental conditions, among the various cell types listed in Table 1, NB4 cells are most sensitive to arsenite in terms of cytotoxicity. A 4-hr 0.25-µM arsenite treatment induces DNA damage but does not affect cell viability (1). A 72-hr, 0.25-µM arsenite treatment does not reduce cell survival, whereas a 72-hr, 2-µM arsenite treatment does.…”

Section: Arsenic Can Induce Dna Damage At Pathologically Meaningful Cmentioning

confidence: 86%

“…However, recent studies have shown that formamidopyrimidine-DNA glycosylase (Fpg) and proteinase K (PK) markedly increase the number of DNA strand breaks (DSB) in arsenite-treated cells (1). Using Fpg-incorporated comet assay, oxidative DNA damage was detected in human vascular smooth muscle cells treated with 1 µM arsenite for 4 hr (2) and in human lymphocytes treated with 10 µM arsenite for 2 hr (3).…”

Section: Arsenic Can Induce Dna Damage At Pathologically Meaningful Cmentioning

confidence: 99%

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Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite.

Bau

Wang

Chung

et al. 2002

Environ Health Perspect

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Arsenic is recognized to be a nonmutagenic carcinogen because it induces DNA damage only at very high concentrations. However, many more DNA strand breaks could be detected by digesting the DNA of arsenite-treated cells with endonuclease III, formamidopyrimidine-DNA glycosylase, and proteinase K. By doing so, arsenite could be shown to induce DNA damage in human cells within a pathologically meaningful concentration range. Oxidized guanine products were detected in all arsenite-treated human cells examined. DNA-protein cross-links were also detected in arsenite-treated NB4 and HL60 cells. In human umbilical vein endothelial cells, the induction of oxidized guanine products by arsenite was sensitive to inhibitors of nitric oxide (NO) synthase but not to oxidant modulators, whereas the opposite result was obtained in vascular smooth muscle cells. On the other hand, the arsenite-induced oxidized guanine products and DNA-protein cross-links in NB4 and HL60 cells were sensitive to modulators of calcium, NO synthase, oxidant, and myeloperoxidase. Therefore, although oxidized guanine products were detected in all the human cells treated with arsenite, the pathways could be different in different cell types. Because the sensitivity and the mechanism of arsenic intoxication are cell specific, it is important that target tissues and target cells are used for investigations. It is also important that pathologically or pharmacologically meaningful concentrations of arsenic are used. This is because in most cases we are dealing with the chronic effect rather than acute toxicity.

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Section: Arsenite Induces Oxidized Guanine Products and Dna-protein Ccontrasting

confidence: 56%

Section: Arsenic Can Induce Dna Damage At Pathologically Meaningful Cmentioning

confidence: 86%

Section: Arsenic Can Induce Dna Damage At Pathologically Meaningful Cmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite.

Bau

Wang

Chung

et al. 2002

Environ Health Perspect

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“…The pathological and therapeutic mechanisms of arsenic are actively debated, and DNA may be an important target for arsenic-related damage. For example, comet assays demonstrate that exposure to as little as 1 nM of sodium arsenite could rapidly (within 30 min) induce DNA base damage in human HeLa, neutrophilic NB4, and HL-60 cells (59,69). For comparison, the reported mean blood arsenic concentration in people consuming highly contaminated water was 560 nM (49), while the mean plasma arsenite concentration for cancer treatment was 1,000 to 6,000 nM (60).…”

mentioning

confidence: 99%

ATF4-Dependent Oxidative Induction of the DNA Repair Enzyme Ape1 Counteracts Arsenite Cytotoxicity and Suppresses Arsenite-Mediated Mutagenesis

Fung

Liu

Demple

2007

Molecular and Cellular Biology

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Arsenite is a human carcinogen causing skin, bladder, and lung tumors, but the cellular mechanisms underlying these effects remain unclear. We investigated expression of the essential base excision DNA repair enzyme apurinic endonuclease 1 (Ape1) in response to sodium arsenite. In mouse 10T 1 ⁄2 fibroblasts, Ape1 induction in response to arsenite occurred about equally at the mRNA, protein, and enzyme activity levels. Analysis of the APE1 promoter region revealed an AP-1/CREB binding site essential for arsenite-induced transcriptional activation in both mouse and human cells. Electrophoretic mobility shift assays indicated that an ATF4/c-Jun heterodimer was the responsible transcription factor. RNA interference targeting c-Jun or ATF4 eliminated arsenite-induced APE1 transcription. Suppression of Ape1 or ATF4 sensitized both mouse fibroblasts (10T 1 ⁄2) and human lymphoblastoid cells (TK6) to arsenite cytotoxicity. Expression of Ape1 from a transgene did not efficiently restore arsenite resistance in ATF4-depleted cells but did offset initial accumulation of abasic DNA damage following arsenite treatment. Mutagenesis by arsenite (at the TK and HPRT loci in TK6 cells) was observed only for ATF4-depleted cells, which was strongly offset by Ape1 expression from a transgene. Therefore, the ATF4-mediated up-regulation of Ape1 and other genes plays a key role against arsenite-mediated toxicity and mutagenesis.Epidemiological studies from Bangladesh, India (West Bengal), Taiwan, and South America indicate that arsenic ingestion, typically via contaminated drinking water, is associated with increased incidence of diverse human diseases, such as atherosclerosis, diabetes, and cancers of the skin, bladder, and lung (55). The arsenic found in drinking water is overwhelmingly one of the inorganic arsenic forms, mostly pentavalent arsenate and trivalent arsenite (55).Arsenite treatment has recently been introduced as therapy for acute promyelocytic leukemia (61). The pathological and therapeutic mechanisms of arsenic are actively debated, and DNA may be an important target for arsenic-related damage. For example, comet assays demonstrate that exposure to as little as 1 nM of sodium arsenite could rapidly (within 30 min) induce DNA base damage in human HeLa, neutrophilic NB4, and HL-60 cells (59, 69). For comparison, the reported mean blood arsenic concentration in people consuming highly contaminated water was 560 nM (49), while the mean plasma arsenite concentration for cancer treatment was 1,000 to 6,000 nM (60). However, many cell-based assays have failed to detect a significant increase in point mutations due to arsenite (55). One conclusion from these observations is that a strong cellular antimutagenesis mechanism counteracts the mutational potential of arsenite-induced DNA damage.Oxidized and other small base lesions are excised by DNA glycosylases, which channel damage into the base excision DNA repair (BER) pathway. In mammalian cells, glycosylase products are processed by the abasic (apurinic/apyrimidinic [AP]) end...

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“…These functions may or may not be related, but both are likely to be required for efficient synapses of broken chromosome ends (26,30). Several reports have shown that As 3+ can induce DNA damage (31,32). Our laboratory has focused on the elucidation of mechanisms explaining how arsenic can act both as a carcinogen and as an effective chemotherapeutic agent (9,33,34).…”

Section: Discussionmentioning

confidence: 99%

Lymphokine-Activated Killer T-Cell-Originated Protein Kinase Phosphorylation of Histone H2AX Prevents Arsenite-Induced Apoptosis in RPMI7951 Melanoma Cells

Zykova

Zhu

et al. 2006

Clinical Cancer Research

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Purpose: Arsenic is a valuable therapeutic tool in cancer treatment. Lymphokine-activated killer T-cell-originated protein kinase (TOPK) is highly expressed in cancer cells, but its specific function is still unknown. We investigated the role of TOPK in arsenic-induced apoptosis in RPMI7951human melanoma cells. Experimental Design: Expression of TOPK was evaluated in different melanoma cell lines, and liquid chromatography-tandem mass spectrometry analysis was used to identify proteins binding with TOPK. Immunofluorescence, Western blot, and flow cytometry were used to assess the effect of arsenic onTOPK, histone H2AX, and apoptosis in RPMI7951cells. Results: Melanoma cell lines expressing high levels of TOPK were more resistant to arsenite (As 3+ )-induced apoptosis. As 3+ treatment induced phosphorylation of TOPK and histone H2AX in RPMI7951human melanoma cells. Liquid chromatography-tandem mass spectrometry results indicated thatTOPK could bind with histone H2AX, and in vitro and in vivo assays confirmed that TOPK binds with and phosphorylates histone H2AX. As 3+ treatment caused phosphorylation of TOPK, which colocalized with phosphorylated histone H2AX in the nucleus. TOPK small interfering RNA cells exhibited a decreased phosphorylation of histone H2AX with As 3+ treatment. As 3+ -induced apoptosis was decreased in H2AX À/À cells but increased in TOPK small interfering RNA cells. Conclusions: TOPK binds with histone H2AX and inhibits As 3+ -induced apoptosis through phosphorylation of histone H2AX. Melanoma cell lines with high levels ofTOPK are more resistant to As 3+ -induced apoptosis. Therefore, inhibition of TOPK activity combined with As 3+ treatment may be helpful in the treatment of melanomas.

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Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian cells

Cited by 113 publications

References 42 publications

Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite.

Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite.

ATF4-Dependent Oxidative Induction of the DNA Repair Enzyme Ape1 Counteracts Arsenite Cytotoxicity and Suppresses Arsenite-Mediated Mutagenesis

Lymphokine-Activated Killer T-Cell-Originated Protein Kinase Phosphorylation of Histone H2AX Prevents Arsenite-Induced Apoptosis in RPMI7951 Melanoma Cells

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