The inherent cellular level of reactive oxygen species: One of the mechanisms determining apoptotic susceptibility of leukemic cells to arsenic trioxide

Though reactive oxygen species (ROS) has been noticed to be involved in arsenic trioxide (As₂O₃)-induced apoptosis of tumor cells, its role in apoptosis signaling remained to be elucidated. The objective of this work was to explore the association of the inherent cellular ROS level with the susceptibility of the tumor cells to apoptosis induction by As₂O₃. Low concentration of As₂O₃ was administered to cultured leukemic cell lines NB4, U937, HL60 and K562. The difference in apoptotic sensitivity was displayed among four cell types. ROS probes were incubated with the cells in the absence of As₂O₃, and ROS was thus quantified relatively by flow cytometry. We manifested, in four cell types, the inherently existed difference in whole ROS quantity, and a positive correlation between the inherent ROS level and their apoptotic sensitivity to As₂O₃. Furthermore, by interference using a ROS producer, we demonstrated that an elevation of ROS level would sensitize the cells to As₂O₃-induced apoptosis. The results of the present work suggested that the inherent ROS level might be determinative in tumor cells for their apoptotic susceptibility to As₂O₃.     

调水调沙工程黄河口近岸沉积物重金属和砷含量的空间分布及其生态风险评估

为了明确调水调沙工程长期影响下黄河口近岸沉积物中重金属含量的分布特征及其生态风险,基于2012年黄河口近岸27个站位的表层沉积物样品,通过ICP-MS测定重金属(Zn、Cr、Ni、Pb、Cu、Cd)和砷(As)含量,并运用潜在生态风险指数法(RI)对其进行生态风险评估。结果表明:近岸沉积物中重金属和As的平均含量表现为AsZnCrNiPbCuCd。Cr、Ni、Cu和Pb四种元素的分布规律较为一致,整体呈现出近岸和近黄河口高而远离河口和岸线低的空间分异特征。Ni、Cu、Pb、Zn与粘土均呈极显著或显著正相关(P0.01或P0.05),而Cd、Cr和As与其相关性均未达到显著水平(P0.05)。近岸沉积物中6种重金属和As的平均单项潜在生态风险指数大小顺序整体表现为CdAsNiPbCuCrZn。就潜在生态风险(RI)而言,研究区域18.52%的站位属轻微生态危害,70.07%的站位属中等生态危害,7.41%的站位属强生态危害,Cd和As是造成危害的两种主要元素。近岸沉积物中重金属和As的来源复杂且多样,主要是由于农业化肥使用、海上石油开采和泄漏、化石燃料燃烧以及河口污染物输入所致。对比研究发现,随着调水调沙工程的长期实施,除Cd和As外沉积物中其他重金属含量均呈下降趋势,说明二者的生态风险将会随调水调沙的长期实施呈增加趋势,而其他重金属的生态风险将呈降低趋势,故未来应重点关注近岸沉积物中Cd和As的生态毒理风险。     

Changes in Bacterial Community Structure and Abundance in Agricultural Soils under Varying Levels of Arsenic Contamination

Arsenic contamination from groundwater used to irrigate crops is a major issue across several agriculturally important areas of Asia. Assessing bacterial community composition in highly contaminated sites could lead to the identification of novel bioremediation strategies. In this study, the bacterial community structure and abundance are assessed in agricultural soils with varying levels of arsenic contamination at Ambagarh Chauki block, Chhattisgarh, India, based on polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) of the 16S rRNA gene and the most probable number-polymerase chain reaction (MPN-PCR). The results revealed that the bacterial communities of arsenic-contaminated soils are dominated by β-proteobacteria (36%), γ-proteobacteria (21%), δ-proteobacteria (11%), α-proteobacteria (11%), and Bacteroidetes (11%). The bacterial composition of high arsenic-contaminated soils differed significantly from that of low arsenic-contaminated soils. The Proteobacteria appeared to be more resistant to arsenic contamination, while the Bacteroidetes and Nitrospirae were more sensitive to it. The bacterial abundance determined by MPN-PCR decreased significantly as As-toxicity increased. In addition to As, other trace metals, like Pb, U, Cu, Ni, Sn, Zn and Zr, significantly ( p < 0.01) explain the changes in bacterial structural diversity in agricultural soils with different level of arsenic contamination, as determined by canonical correspondence analysis (CCA).     

Distribution of Arsenite-Oxidizing Bacteria and its Correlation with Temperature in Hot Springs of the Tibetan-Yunnan Geothermal Zone in Western China

The distribution of arsenite-oxidizing bacteria in response to temperature is of great importance to an understanding of biogeochemical cycling of arsenic in geothermal features. The abundance and diversity of arsenite-oxidizing bacteria were investigated in the geothermal features of Tengchong County of Yunnan Province, Dachaidan County of Qinghai Province, and Tibet. The abundance of aioA genes, which encode the large subunit of arsenite oxidase, was determined by quantitative polymerase chain reactions. The diversity of aioA genes was studied by PCR-cloning-based phylogenetic analyses. The results showed that the aioA gene abundance increased as temperature decreased, whereas its diversity at the OTU level (97% cutoff) increased with increasing temperature. This suggests that temperature played an important role in affecting aioA gene distribution and thus arsenic speciation. The aioA gene population (at OTU level) differed among the studied regions, indicating geographic isolation may be an important factor controlling aioA gene distribution in hot springs.     

Microbial Diversity in a Pyrite-Rich Tailings Impoundment (Carnoulès,France)

The microbial communities have been investigated in the subsurface waters of the Carnoulès pyrite-rich tailings impoundment (France) for two hydrological situations characterized by the presence of oxygenated waters during winter and suboxic conditions in early autumn. In these acidic waters (2–5) characterized by elevated concentrations of Fe (1608–3354 mg · l^?1), As (130–434 mg · l^?1) and sulfates (5796–14318 mg · l^?1) and variable dissolved oxygen content, the cultivable bacteria found in these system are Thiomonas and Acidithiobacillus ferrooxidans. Molecular methods, Terminal-Restriction Fragment Length Polymorphism (T-RFLP), and 16S rRNA encoding gene library analysis indicate low diversity. The environment is dominated by only a few types of microorganisms, with 70–80% of the whole bacterial population assigned to two or three Terminal-Restriction Fragments (T-RFs). Most of these organisms are uncultured, newly described, or recently associated with acid mine drainage. Modifications of the community structure are observed as a function of the sampling period and seem to be related to the aqueous chemistry of the tailings water. At low Dissolved Oxygen (DO = 1 mg · l^?1) concentrations and moderately acidic conditions (pH = 5.7), the dominant organisms are related to the uncultured clone BA31 affiliated with Desulfosarcina variabilis, a sulfate-reducing bacteria (SRB), Acidithiobacillus ferrooxidans and the uncultured clone BVB20, closely related to Thiobacillus. At high (12 mg · l^?1) DO concentrations and low (< 2) pH values, the microbial diversity is less important and 65% of the population is assigned to the uncultured bacterium clone AS6 related to Desulfosarcina variabilis.     

Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh

Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p≤0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p ≤ 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions.     

Phosphorus Improves Arsenic Phytoremediation by Anadenanthera Peregrina by Alleviating Induced Oxidative Stress

Due to similarities in their chemical behaviors, studies examining interactions between arsenic (As)—in special arsenate—and phosphorus (P) are important for better understanding arsenate uptake, toxicity, and accumulation in plants. We evaluated the effects of phosphate addition on plant biomass and on arsenate and phosphate uptake by Anadenanthera peregrina, an important Brazilian savanna legume. Plants were grown for 35 days in substrates that received combinations of 0, 10, 50, and 100 mg kg^?1 arsenate and 0, 200, and 400 mg kg^?1 phosphate. The addition of P increased the arsenic-phytoremediation capacity of A. peregrina by increasing As accumulation, while also alleviating As-induced oxidative stress. Arsenate phytotoxicity in A. peregrina is due to lipid peroxidation, but not hydrogen peroxide accumulation. Added P also increased the activity of important reactive oxygen species-scavenging enzymes (catalase and ascorbate peroxidase) that help prevent lipid peroxidation in leaves. Our findings suggest that applying P represents a feasible strategy for more efficient As phytoremediation using A. peregrina.     

BCR-ABL1-induced leukemogenesis and autophagic targeting by arsenic trioxide

We have recently shown that arsenic trioxide (As₂O₃) is a potent inducer of autophagic degradation of the BCR-ABL1 oncoprotein, which is the cause of chronic myeloid leukemia (CML) and Ph+ acute lymphoid leukemia (Ph+ ALL). Our recently published work has shown that pharmacological inhibition of autophagy or molecularly targeting of elements of the autophagic machinery partially reverses the suppressive effects of As₂O₃ on primitive leukemic precursors from CML patients. Altogether, our studies have provided direct evidence that arsenic-induced, autophagy-mediated, degradation of BCR-ABL1 is an important mechanism for the generation of the effects of As₂O₃ on BCR-ABL1 transformed leukemic progenitors. These studies raise the potential of future clinical-translational efforts employing combinations of arsenic trioxide with autophagy-modulating agents to promote elimination of early leukemic progenitors and, possibly, leukemia-initiating stem cells.