Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL patients over three consecutive days. The patients received 10 mg arsenic trioxide each day via intravenous infusion. The saliva samples were analyzed using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Monomethylarsonous acid and monomethylmonothioarsonic acid were identified along with arsenite, dimethylarsinic acid, monomethylarsonic acid, and arsenate. Arsenite was the predominant arsenic species, accounting for 71.8 % of total arsenic in the saliva. Following the arsenic infusion each day, the percentage of methylated arsenicals significantly decreased, possibly suggesting that the arsenic methylation process was saturated by the high doses immediately after the arsenic infusion. The temporal profiles of arsenic species in saliva following each arsenic infusion over 3 days have provided information on arsenic exposure, metabolism, and excretion. These results suggest that saliva can be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients. [Figure: see text

Chromium on the Hands of Children After Playing in Playgrounds Built from Chromated Copper Arsenate (CCA)–Treated Wood

Children’s exposure to arsenic and chromium from playground equipment constructed with chromated copper arsenate (CCA)–treated wood is a potential concern because of children’s hand-to-mouth activity. However, there exists no direct measure of Cr levels on the hands of children after playing in such playgrounds. In this study we measured both soluble and total Cr on the hands of 139 children playing in playgrounds, eight of which were constructed with CCA-treated wood and eight of which were not. Children’s age and duration of play were recorded. The hands of each child were washed after play with 150 mL deionized water, which was collected in a bag and subsequently underwent analysis of Cr and 20 other elements, using inductively coupled plasma mass spectrometry. Total average Cr on the hands of 63 children who played in CCA playgrounds was 1,112 ± 1,089 ng (median, 688; range 78–5,875). Total average Cr on the hands of 64 children who played in non-CCA playgrounds was 652 ± 586 ng (median, 492; range 61–3,377). The difference between the two groups is statistically significant (p < 0.01). Cr levels were highly correlated to both Cu (r = 0.672) and As (r = 0.736) levels in CCA playgrounds (p ≤ 0.01), but not non-CCA playgrounds (r = 0.252 and 0.486 for Cu and As, respectively). Principal-component analysis indicates that Cr, Cu, and As are more closely grouped together in CCA than in non-CCA playgrounds. These results suggest that the elevated levels of Cr and As on children’s hands are due to direct contact with CCA wood

Chronic Arsenic Exposure and Oxidative Stress: OGG1 Expression and Arsenic Exposure, Nail Selenium, and Skin Hyperkeratosis in Inner Mongolia

Arsenic, a human carcinogen, is known to induce oxidative damage to DNA. In this study we investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for an enzyme, 8-oxoguanine DNA glycosylase, involved in removing 8-oxoguanine in As-exposed individuals. Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Water, toenail, and blood samples were collected from 299 Ba Men residents exposed to 0.34–826 μg/L As. RNA was isolated from blood, and mRNA levels of OGG1 were determined using real-time polymerase chain reaction. OGG1 expression levels were linked to As concentrations in drinking water and nails, selenium concentrations in nails, and skin hyperkeratosis. OGG1 expression was strongly associated with water As concentrations (p < 0.0001). Addition of the quadratic term significantly improved the fit compared with the linear model (p = 0.05). The maximal OGG1 response was at the water As concentration of 149 μg/L. OGG1 expression was also significantly associated with toenail As concentrations (p = 0.015) but inversely associated with nail Se concentrations (p = 0.0095). We found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age even though the oldest group showed the strongest OGG1 response (p = 0.0001). OGG1 expression showed a dose-dependent increased risk of skin hyperkeratosis in males (trend analysis, p = 0.02), but the trend was not statistically significant in females. The results from this study provide a linkage between oxidative stress and As exposure in humans. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure

Cardiovascular disease and arsenic exposure in Inner Mongolia, China: a case control study

BackgroundMillions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in highly exposed populations and lacked individual measurements.ObjectiveTo evaluate the association between cardiovascular disease and well-water arsenic exposure.MethodsWe conducted a hospital based case control study in Inner Mongolia, China. Cases and controls were prospectively identified and enrolled from a large hospital in the Hangjin Hou area. Cases were patients diagnosed with cardiovascular disease and controls were patients free from cardiovascular disease, admitted for conditions unrelated to arsenic exposure. Water from the primary water source and toenail samples were collected from each subject and tested for inorganic arsenic.ResultsArsenic exposures were moderate with mean and median arsenic exposures of 8.9μg/L and 13.1μg/L, respectively. A total of 298 cases and 275 controls were enrolled. The adjusted odds ratio (AOR) and corresponding 95% confidence interval (95% CI) for a 10μg/L increase in water arsenic were 1.19 (95% CI: 1.03, 1.38). Compared to exposures less than 10μg/L, the AOR for water arsenic exposures above 40μg/L was 4.05 (95% CI: 1.1-14.99, p = 0.04). Nail arsenic above 1.38μg/g was also associated with an increased risk of cardiovascular disease.ConclusionsBy using standardized case definitions and collecting individual measurements of arsenic, this study addressed several limitations of previous studies. The results provide further evidence of the association between cardiovascular disease and arsenic at moderate exposures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-015-0022-y) contains supplementary material, which is available to authorized users

Arsenic on the Hands of Children after Playing in Playgrounds

Increasing concerns over the use of wood treated with chromated copper arsenate (CCA) in playground structures arise from potential exposure to arsenic of children playing in these playgrounds. Limited data from previous studies analyzing arsenic levels in sand samples collected from CCA playgrounds are inconsistent and cannot be directly translated to the amount of children’s exposure to arsenic. The objective of this study was to determine the quantitative amounts of arsenic on the hands of children in contact with CCA-treated wood structures or sand in playgrounds. We compared arsenic levels on the hands of 66 children playing in eight CCA playgrounds with levels of arsenic found on the hands of 64 children playing in another eight playgrounds not constructed with CCA-treated wood. The children’s age and duration of playtime were recorded at each playground. After play, children’s hands were washed in a bag containing 150 mL of deionized water. Arsenic levels in the hand-washing water were quantified by inductively coupled plasma mass spectrometry. Our results show that the ages of the children sampled and the duration of play in the playgrounds were similar between the groups of CCA and non-CCA playgrounds. The mean amount of water-soluble arsenic on children’s hands from CCA playgrounds was 0.50 μg (range, 0.0078–3.5 μg). This was significantly higher (p < 0.001) than the mean amount of water-soluble arsenic on children’s hands from non-CCA playgrounds, which was 0.095 μg (range, 0.011–0.41 μg). There was no significant difference in the amount of sand on the children’s hands and the concentration of arsenic in the sand between the CCA and non-CCA groups. The higher values of arsenic on the hands of children playing in the CCA playgrounds are probably due to direct contact with CCA-treated wood. Washing hands after play would reduce the levels of potential exposure because most of the arsenic on children’s hands was washed off with water. The maximum amount of arsenic on children’s hands from the entire group of study participants was < 4 μg, which is lower than the average daily intake of arsenic from water and food

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism