Risk and Revisionism in Arsenic Cancer Risk Assessment

Mushak, Paul; Crocetti, Annemarie F.

doi:10.2307/3432859

Cited by 24 publications

(20 citation statements)

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“…A century ago, arsenic was recommended as an antileukemic agent; however its use was abandoned because of toxicity. More recently, arsenic trioxide, the anhydrous form of As(OH) 3 (Trisenox, Cell Therapeutics, Seattle) has been approved as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia (39,40). Our study suggests that AQP9 may be responsible for the chemotherapeutic effects of arsenite by facilitating diffusion of the agent into the leukemia cells.…”

Section: Discussionmentioning

confidence: 73%

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Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Liu

Shen

Carbrey

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

459

298

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Much is known about the transport of arsenite and antimonite into microbes, but the identities of mammalian transport proteins are unknown. The Saccharomyces cerevisiae FPS1 gene encodes a membrane protein homologous to the bacterial aquaglyceroporin GlpF and to mammalian aquaglyceroporins AQP7 and AQP9. Fps1p mediates glycerol uptake and glycerol efflux in response to hypoosmotic shock. Fps1p has been shown to facilitate uptake of the metalloids arsenite and antimonite, and the Escherichia coli homolog, GlpF, facilitates the uptake and sensitivity to metalloid salts. In this study, the ability of mammalian aquaglyceroporins AQP7 and AQP9 to substitute for the yeast Fps1p was examined. The fps1⌬ strain of S. cerevisiae exhibits increased tolerance to arsenite and antimonite compared to a wild-type strain. Introduction of a plasmid containing AQP9 reverses the metalloid tolerance of the deletion strain. AQP7 was not expressed in yeast. The fps1⌬ cells exhibit reduced transport of 73 As(III) or 125 Sb(III), but uptake is enhanced by expression of AQP9. Xenopus laevis oocytes microinjected with either AQP7 or AQP9 cRNA exhibited increased transport of 73 As(III). These results suggest that AQP9 and AQP7 may be a major routes of arsenite uptake into mammalian cells, an observation potentially of large importance for understanding the action of arsenite as a human toxin and carcinogen, as well as its efficacy as a chemotherapeutic agent for acute promyelocytic leukemia.Fps1p ͉ GlpF ͉ acute promyelocytic leukemia

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Section: Discussionmentioning

confidence: 73%

“…Most of the epidemiological studies have been conducted in countries such as Taiwan, Bangladesh, and Chile, where arsenic exposure is endemic (39,40). Chronic effects of arsenic in the water supply include skin hyperpigmentation and keratoses of the hands and feet that frequently progress to skin cancers.…”

Section: Discussionmentioning

confidence: 99%

Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Liu

Shen

Carbrey

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

459

298

View full text Add to dashboard Cite

show abstract

“…Animal studies show that the bioavailability of S-adenosylmethionine, the source of methyl groups for arsenic methylation, is not a limiting factor for methylation under normal in vivo conditions (31), but it has been suggested that high arsenic exposure may cause the demand for methyl groups to exceed the supply, particularly for individuals with a diet poor in methionine (18). However, it was estimated that exposures to an arsenic concentration of 1800 pg/l in drinking water would require only 1.5% of a person's daily dietary intake of methyl source for arsenic methylation (49), making it unlikely that the supply of methyl groups would be exceeded. Nevertheless, there may be a limited supply of methyltransferases or other chemicals involved in both arsenic and DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

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“…We respond to Mushak and Crocetti's recent publication (1), which criticizes several of our recently published analyses related to arsenic cancer risk assessment (2)(3)(4)(5). Basically, their criticism is that evidence of an overestimate of arsenic risk using the present cancer slope factor (CSF) is poorly supported.…”

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confidence: 99%

“…The impact of protein deficiency on arsenic methylation may be a factor in explaining differential susceptibility to arsenic across populations. Mushak and Crocetti (1) conclude that this is not likely to be an important factor based on a calculation of the molar ratio of arsenic to methionine and cysteine intake in the Taiwanese population, indicating that less than 1% of the daily donor methyl availability would be required to completely methylate total available arsenic. However, a study in rabbits suggests that even a 67-to 100-fold excess in the molar quantity of donor methyl compounds, as was estimated for the Taiwanese population, is within the range capable of affecting arsenic methylation.…”

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confidence: 99%