Evidence that arsenite acts as a cocarcinogen in skin cancer

Rossman, Toby G.; Uddin, Ahmed; Burns, Fredric J.

doi:10.1016/j.taap.2003.10.016

Cited by 221 publications

(154 citation statements)

References 126 publications

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“…Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis [13,14]. The mode-of-action studies suggest that the arsenic might be acting as a cocarcinogen, a promoter or a progressor of carcinogensis [15].…”

Section: Mechanisms Of Arsenic Carcinogenesismentioning

confidence: 99%

“…K + MN are usually derived from whole chromosome and are induced by agents that cause aneuploidy, whereas X-rays and other clastogens induce (K ) ) MN [39,40]. Therefore at low dose, arsenite acts as an aneugen, but at high dose it acts as a clastogen [15]. An increased frequency of MN has been detected in exfoliated bladder cells, buccal cells, sputum cells and lymphocytes from arsenic-exposed population [41][42][43].…”

Section: Genotoxicitymentioning

confidence: 99%

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Arsenic Carcinogenesis in the Skin

2006

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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

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Section: Mechanisms Of Arsenic Carcinogenesismentioning

confidence: 99%

Section: Genotoxicitymentioning

confidence: 99%

Arsenic Carcinogenesis in the Skin

2006

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“…They found that an average 88% of the biological samples contain arsenic above the normal level. Though chronic arsenic poisoning is manifested primarily in skin lesions, it can induce health problems such as melanosis, leukomelanosis, hyperkeratosis, cardiovascular disease, hepatomegaly, neuropathy, diabetes mellitus, adverse pregnancy outcomes, impaired child development, hypertension, respiratory problems and cancer (CHEn et al, 2007a;CHEn et al, 2007b;HADI and PARVEEn, 2004;MILtOn et al, 2001;ROssMAn et al, 2004). Moreover, a study reports that presence of arsenic during DnA synthesis can induce chromosomal aberrations, sister chromatid exchanges and malsegragation of chromosomes (nAtARAJAn et al, 1996, cited in kARIM, 2000.…”

Section: Arsenic Induced Health Hazardsmentioning

confidence: 99%

Arsenic mitigation measures in Bangladesh

Khan¹

2012

rseau

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The scale of arsenic toxicity of the groundwater in Bangladesh is greater than any environmental debacle in the history of human civilization. The main route of arsenic accumulation in the human body is the ingestion of arsenic tainted water. Because of the undetectable nature of arsenic poisoning at the early stage and lack of awareness due to mass illiteracy, poverty and malnutrition, arsenic related ailments may cause death. However, this paper mainly discusses arsenic mitigation measures in Bangladesh. Although a piped surface water supply after treatment is the absolute solution to get rid of this crisis, the weak economic background of Bangladesh does not support supplying such water to every corner of rural areas. Hence research groups have developed their own methods to suit the local environment, using locally available materials and approaches based on the common method of arsenic removal: use of oxidizing agents, followed by flocculation and precipitation. Again, among different alternative water supply options, deep tubewells, which have been used by the communities in Bangladesh during the past few decades, appear to be a more suitable alternate option. Moreover, household-based arsenic filters can be a good choice if proper maintenance can be done.L’accroissement du problème de toxicité causé par l’arsenic au Bangladesh constitue une catastrophe environnementale majeure dans l’histoire de l’humanité. La principale voie d’accumulation de l’arsenic dans le corps humain est l’ingestion d’eau polluée par ce contaminant. La nature indétectable de l’empoisonnement à l’arsenic dans les premières étapes, l’insuffisance d’avertissement attribuable à l’analphabétisme, ainsi qu’à la pauvreté et la malnutrition, font en sorte que l’empoisonnement progressif à l’arsenic peut causer la mort. Le présent article discute toutefois les mesures d’atténuation envisagées au Bangladesh. Ainsi, bien que l’alimentation dans des conduites avec de l’eau de surface traitée représente la solution idéale pour résoudre cette crise, l’état économique précaire du Bangladesh ne permet pas d’alimenter en eau de surface traitée toutes les populations des zones rurales. De là, des groupes de recherche ont développé des méthodes spécifiques à l’environnement local en utilisant des matériaux disponibles sur place et basées sur une méthode établie d’enlèvement de l’arsenic : en utilisant des agents oxydants suivi par la floculation et la précipitation. Parmi les différentes alternatives d’alimentation en eau explorées, la technique de puits profonds, laquelle a été utilisée par les communautés au Bangladesh durant les décennies passées, apparaît être l’option la plus appropriée. De plus, l’emploi d’unités de filtration dans les résidences peut être un bon choix, dans les cas où celles-ci sont entretenues adéquatement

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“…Arsenic compounds were the only compounds that IARC considered to have sufficient evidence for human carcinogenicity. Some studies confirm that arsenite is not significantly mutagenic in bacterial or mammalian cell detection systems, so it is sometimes considered a tumor promoter and, more recently, was shown to be a co-carcinogen in mouse models [4,5]. Other studies show that arsenite is a complete transplacental carcinogen in mice [6], while dimethylarsinic acid, a major metabolite of arsenic in most mammals, including humans, causes bladder cancer in F344 rats [7].…”

Section: Introductionmentioning

confidence: 99%

Altered iron homeostasis involvement in arsenite-mediated cell transformation

Eckard

Chen

et al. 2006

Free Radical Biology and Medicine

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Chronic exposure to low doses of arsenite causes transformation of human osteogenic sarcoma (HOS) cells. Although oxidative stress is considered important in arsenite-induced cell transformation, the molecular and cellular mechanisms by which arsenite transforms human cells are still unknown. In the present study, we investigated whether altered iron homeostasis, known to affect cellular oxidative stress, can contribute to the arsenite-mediated cell transformation. Using arsenite-induced HOS cell transformation as a model, it was found that total iron levels are significantly higher in transformed HOS cells in comparison to parental control HOS cells. Under normal iron metabolism conditions, iron homeostasis is tightly controlled by inverse regulation of ferritin and transferrin receptor (TfR) through iron regulatory proteins (IRP). Increased iron levels in arsenite transformed cells should theoretically lead to higher ferritin and lower TfR in these cells than in controls. However, the results showed that both ferritin and TfR are decreased, apparently through two different mechanisms. A lower ferritin level in cytoplasm was due to the decreased mRNA in the arsenitetransformed HOS cells, while the decline in TfR was due to a lowered IRP-binding activity. By challenging cells with iron, it was further established that arsenite-transformed HOS cells are less responsive to iron treatment than control HOS cells, which allows accumulation of iron in the transformed cells, as exemplified by significantly lower ferritin induction. On the other hand, caffeic acid phenethyl ester (CAPE), an antioxidant previously shown to suppress As-mediated cell transformation, prevents As-mediated ferritin depletion. In conclusion, our results suggest that altered iron homeostasis contributes to arsenite-induced oxidative stress and, thus, may be involved in arsenite-mediated cell transformation.

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Evidence that arsenite acts as a cocarcinogen in skin cancer

Cited by 221 publications

References 126 publications

Arsenic Carcinogenesis in the Skin

Arsenic Carcinogenesis in the Skin

Arsenic mitigation measures in Bangladesh

Altered iron homeostasis involvement in arsenite-mediated cell transformation

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