Sodium arsenite potentiates the clastogenicity and mutagenicity of dna crosslinking agents

Lee, T C; Lee, K C; Tzeng, Yin-Jeh; Huang, Ruea‐Yea; Jan, K Y

doi:10.1002/em.2860080111

Cited by 65 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although evidence for their induction of tumors in experimental animals is still insufficient [IARC, 1980;Leonard and Lauwerys, 1980;Goyer, 19861, arsenic compounds induce sister chromatid exchanges, chromosome aberrations, and gene amplification in a variety of in vitro systems [Zanzoni and Jung, 1980;Larramendy et al, 1981; Lee et al, 1985Lee et al, , 1986. However, the mechanism of arsenic carcinogenicity is still obscure.…”

Section: Introductionmentioning

confidence: 98%

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

Huang

Yih

et al. 1995

Environ and Mol Mutagen

View full text Add to dashboard Cite

Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 microM) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplication in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity.

show abstract

Section: Introductionmentioning

confidence: 98%

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

Huang

Yih

et al. 1995

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…Interfering of these DNA repair proteins by arsenic is shown to affect genome stabilities of the cells. Arsenite enhances the mutagenicity of carcinogeneic stresses (such as UV, X-rays, and chemical agent) in mammalian cells [52][53][54][55]. It is proposed that spontaneous or induced mutations in key genetic sites can then lead to subsequent mutation via inhibited DNA repair by arsenic.…”

Section: Altered Dna Repairmentioning

confidence: 99%

Arsenic Carcinogenesis in the Skin

2006

View full text Add to dashboard Cite

SummaryChronic arsenic poisoning is a world public health issue. Long-term exposure to inorganic arsenic (As) from drinking water has been documented to induce cancers in lung, urinary bladder, kidney, liver and skin in a dose-response relationship. Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure. There are significant associations between these dermatological lesions and risk of skin cancer. The most common arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase-8 signaling, respectively. Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an inhibitory effect on proliferation. As-UVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sun-exposed skin. The multiple and recurrent skin lesions are associated with cellular immune dysfunction in chronic arsenism. A decrease in peripheral CD4+ cells was noticed in the inhabitants of arsenic exposure areas. There was a decrease in the number of Langerhans cells in As-BD lesion which results in an impaired immune function on the lesional sites. Since CD4+ cells are the target cell affected by As, the interaction between CD4+ cells and epidermal keratinocytes under As affection might be closely linked to the pathogenesis of multiple occurrence of arsenic-induced skin cancer. In this

show abstract

“…In the case of tumors in mice that drank water with As 3þ , the tumor microenvironment would be affected by the systemic level of As 3þ in the animal, as suggested by Laconia, Doratiottoa, and Vineis (2008). Alterations at a genomic level in tumor cells can be enhanced by the mutagenic effect of As 3þ and its deleterious action on DNA repair mechanisms (Lee, Oshimura, and Barrett 1985;Lee et al 1986;Yang et al 1992;Rossman 2003;Guillamet et al 2004), which would favor the tumor progression phase, as is reflected in the higher conversion index.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sodium Arsenite on Mouse Skin Carcinogenesis

Palmieri

Molinari

2015

Toxicol Pathol

View full text Add to dashboard Cite

Arsenic is carcinogenic in human beings, and environmental exposure to arsenic is a public health issue that affects large populations worldwide. Thus, studies are needed to determine the mode of action of arsenic and prevent harmful effects arising from arsenic intake. The present study assessed the influence of sodium arsenite (As 3þ ) on potentially carcinogenic processes that are either pre-existing or concomitant with chronic intake of water containing As 3þ . Experiments using SENCAR mice were designed to evaluate the effect of chronic administration of As 3þ (2, 20, or 200 mg of As 3þ /L) in drinking water that overlapped to varying degrees with a 2-stage carcinogenesis protocol carried out over 9 months. The results showed a time-dependent pattern. During early stages of carcinogenesis (6-12 weeks), animals exposed to As 3þ and the carcinogenesis protocol showed increased numbers of tumors compared to control animals. During late carcinogenesis (16-30 weeks), the number of tumors stabilized to below control values, but the tumors showed increased malignancy. These findings indicate that the outcomes of the 2-stage skin carcinogenesis protocol are modified by the presence of arsenite in drinking water, which increases the rate of carcinoma development.

show abstract

Sodium arsenite potentiates the clastogenicity and mutagenicity of dna crosslinking agents

Cited by 65 publications

References 35 publications

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

Arsenic Carcinogenesis in the Skin

Effect of Sodium Arsenite on Mouse Skin Carcinogenesis

Contact Info

Product

Resources

About