Oxidative stress as a possible mode of action for arsenic carcinogenesis

Gene expression changes in primary human uroepithelial cells exposed to arsenite and its methylated metabolites were evaluated to identify cell signaling pathway perturbations potentially associated with bladder carcinogenicity. Cells were treated with mixtures of inorganic arsenic and its pentavalent or trivalent metabolites for 24 hr at total arsenic concentrations ranging from 0.06 lM to 18 lM. One series (five samples) was conducted with arsenite and pentavalent metabolites and a second (10 samples) with arsenite and trivalent metabolites. Similar gene expression responses were obtained for pentavalent or trivalent metabolites. A suite of eight gene changes was consistently identified across individuals that reflect effects on key signaling pathways: oxidative stress, protein folding, growth regulation, metallothionine regulation, DNA damage sensing, thioredoxin regulation, and immune response. No statistical significance of trend (NOSTASOT) analysis of these common genes identified lowest observed effect levels (LOELs) from 0.6 to 6.0 lM total arsenic and no observed effect levels (NOELs) from 0.18 to 1.8 lM total arsenic. For the trivalent arsenical mixture, benchmark doses (BMDs) ranged from 0.13 to 0.92 lM total arsenic; benchmark dose lower 95% confidence limits (BMDLs) ranged from 0.09 to 0.58 lM total arsenic. BMDs ranged from 0.53 to 2.7 lM and BMDLs from 0.35 to 1.7 lM for the pentavalent arsenical mixture. Both endpoints varied by a factor of 3 across individuals. This study is the first to examine gene expression response in primary uroepithelial cells from multiple individuals and to identify no effect levels for arsenical-induced cell signaling perturbations in normal human cells exposed to a biologically plausible concentration range.Environ. Mol. Mutagen. 54:82-98, 2013. V V C 2012 Wiley Periodicals, Inc.

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“…DOI 10.1002/em concentrations [Kitchin and Ahmad, 2003]. Results in the present study are concordant with these findings.…”

Section: Discussionsupporting

confidence: 93%

Evaluation of gene expression changes in human primary uroepithelial cells following 24‐Hr exposures to inorganic arsenic and its methylated metabolites

Yager

Gentry

Thomas

et al. 2012

Environ and Mol Mutagen

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“…Arsenic is well known for the production of reactive oxygen species (ROS) [13,14]. In normal healthy body ROS and antioxidants remain in balance, and when this balance is disturbed, oxidative stress occurs [15].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Arsenic Induced DNA Fragmentation by using Comet Assay

Mahjabeen¹

2016

J Carcinog Mutagen

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Arsenic is metalloid present in measureable quantity in air, water, and soil through natural and anthropogenic sources. It is neurotoxic, hepatotoxic and genotoxic effects, variety of health problems have been associated to arsenic exposure. This review was designed to investigate the possible association between arsenic exposure and DNA damage in animals and humans using comet assay. Total 28 studies were selected for measuring DNA damage by comet assay. Trend of significance in tail length and tail moment was observed using regression analysis. Due to limited number of studies available the regression analysis was non-significant. Individually each study suggested a significant increase in tail moment and tail length in a dose and time-dependent manner. Overall trend observed in this review is the positive association between arsenic exposure either experimentally or occupationally and DNA damage. This initial effort may provide future guideline for the assessment of DNA fragmentation using comet assay.

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“…Arsenic is a cause of great health concern throughout the world, as it is believed to be related to cardiovascular 1 , gastrointestinal 2 , respiratory 3 , skin 4 , endocrine 5 disorders and carcinogenesis 6 . It has been classified by WHO as Group I carcinogen 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Nutritional status also facilitates the first and second stage methylation and excretion of inorganic arsenic 14 , some nutrients such as vitamin E 15 , folic acid 16 , selenium 17 , B 6 , B 12 , zinc 18 play an important role in this aspect. Human beings are being chronically exposed to inorganic arsenic through food and drinking water, a major cause of disease and disability.…”

mentioning

confidence: 99%

Inhibitory effect of arsenic on aerobic gut flora in rat

Choudhry

Misbahuddin

Hossain

et al. 2010

Bangladesh Med Res Counc Bull

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An in vivo study was carried on rats to see the influence of arsenic on aerobic gut flora. A significant inhibition of gut flora was observed after 2 weeks of administration of arsenic (1 mg/L) ad libitum with a decrease in stool arsenic level and increase in liver arsenic level. However, this inhibitory effect of arsenic on gut flora was not observed in presence of vitamin E (1 mg/day) or selenium (0.4 µg/day). Pretreatment with streptomycin (500 mg twice daily) showed similar results. Rats that received folic acid (200 µg/day) showed inhibition of gut floral count but there were decreased liver arsenic level.

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Oxidative stress as a possible mode of action for arsenic carcinogenesis

Cited by 254 publications

References 35 publications

Evaluation of gene expression changes in human primary uroepithelial cells following 24‐Hr exposures to inorganic arsenic and its methylated metabolites

Evaluation of gene expression changes in human primary uroepithelial cells following 24‐Hr exposures to inorganic arsenic and its methylated metabolites

Assessment of Arsenic Induced DNA Fragmentation by using Comet Assay

Inhibitory effect of arsenic on aerobic gut flora in rat

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