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

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

An Emerging Role for Epigenetic Dysregulation in Arsenic Toxicity and Carcinogenesis

Competing Interests Declaration: The authors declare they have no competing financial interests. Abbreviations: AHCY, S-adenosylhomocysteine hydrolase; APL, acute promyelocytic leukemias; As, inorganic arsenic; AS3MT, arsenic (+3 oxidation state) methyltransferase; ChIP-on-chip, chromatin immunoprecipitation-on-chip; ChIP-seq, chromatin immunoprecipitation-sequencing; DEFB1, defensin, beta 1; DNMTs, DNA methyltransferases; H3K4me3, H3K4 tri-methylation; H3K9me2, H3K9 di-methylation; H3K27me3, H3K27 tri-methylation; HATs, histone acetyltransferases; HDACs, histon

Genetic integrity of the human Y chromosome exposed to groundwater arsenic

<p>Abstract</p> <p>Background</p> <p>Arsenic is a known human carcinogen reported to cause chromosomal deletions and genetic anomalies in cultured cells. The vast human population inhabiting the Ganges delta in West Bengal, India and Bangladesh is exposed to critical levels of arsenic present in the groundwater. The genetic and physiological mechanism of arsenic toxicity in the human body is yet to be fully established. In addition, lack of animal models has made work on this line even more challenging.</p> <p>Methods</p> <p>Human male blood samples were collected with their informed consent from 5 districts in West Bengal having groundwater arsenic level more than 50 μg/L. Isolation of genomic DNA and preparation of metaphase chromosomes was done using standard protocols. End point PCR was performed for established sequence tagged sites to ascertain the status of recombination events. Single nucleotide variants of candidate genes and amplicons were carried out using appropriate restriction enzymes. The copy number of DYZ1 array per haploid genome was calculated using real time PCR and its chromosomal localization was done by fluorescence in-situ hybridization (FISH).</p> <p>Results</p> <p>We studied effects of arsenic exposure on the human Y chromosome in males from different areas of West Bengal focusing on known recombination events (P5-P1 proximal; P5-P1 distal; gr/gr; TSPY-TSPY, b1/b3 and b2/b3), single nucleotide variants (SNVs) of a few candidate Y-linked genes (DAZ, TTY4, BPY2, GOLGA2LY) and the amplicons of AZFc region. Also, possible chromosomal reorganization of DYZ1 repeat arrays was analyzed. Barring a few microdeletions, no major changes were detected in blood DNA samples. SNV analysis showed a difference in some alleles. Similarly, DYZ1 arrays signals detected by FISH were found to be affected in some males.</p> <p>Conclusions</p> <p>Our Y chromosome analysis suggests that the same is protected from the effects of arsenic by some unknown mechanisms maintaining its structural and functional integrities. Thus, arsenic effects on the human body seem to be different compared to that on the cultured cells.</p

Novel therapeutic approach: organic arsenical (melarsoprol) alone or with all-trans -retinoic acid markedly inhibit growth of human breast and prostate cancer cells in vitro and in vivo

The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently, another arsenical, As2O3was shown to be effective in treatment of acute promyelocytic leukaemia. We have investigated the anti-tumour activities of Mel-B either with or without all-trans -retinoic acid (ATRA) using the MCF-7 human breast cancer cells, as well as the PC-3 and DU 145 human prostate cancer cells both in vitro and in vivo. The antiproliferative effects of Mel-B and/or ATRA against breast and prostate cancer were tested in vitro using clonogenic assays and in vivo in triple immunodeficient mice. Furthermore, the mechanism of action of these compounds was studied by examining the cell cycle, levels of bcl-2, apoptosis and antiproliferative potency using a pulse-exposure assay. Clonogenic assays showed that the cancer cell lines were sensitive to the inhibitory effect of Mel-B (effective dose that inhibited 50% clonal growth [ED50]: 7 × 10−9M for MCF-7, 2 × 10−7M for PC-3, 3 × 10−7M for DU145 cells. Remarkably, the combination of Mel-B and ATRA had an enhanced antiproliferative activity against all three cancer cell lines. Furthermore, the combination of Mel-B and ATRA induced a high level of apoptosis in all three cell lines. Treatment of PC-3 and MCF-7 tumours growing in triple immunodeficient mice with Mel-B and ATRA either alone or in combination markedly retarded tumour size and weight of the tumours without major side-effects. In conclusion, our results suggest that either Mel-B alone or with ATRA may be a useful, novel therapy for breast and prostate cancers. © 2000 Cancer Research Campaig

Induction of JNK and c-Abl signalling by cisplatin and oxaliplatin in mismatch repair-proficient and -deficient cells

Loss of DNA mismatch repair has been observed in a variety of human cancers. Recent studies have shown that loss of DNA mismatch repair results in resistance to cisplatin but not oxaliplatin, suggesting that the mismatch repair proteins serve as a detector for cisplatin but not oxaliplatin adducts. To identify the signal transduction pathways with which the detector communicates, we investigated the effect of loss of DNA mismatch repair on activation of known damage-responsive pathways, and recently reported that cisplatin differentially activates c-Jun NH2-terminal kinase (JNK) and c-Abl in repair-proficient vs.-deficient cells. In the current study, we directly compared differential activation of these pathways by cisplatin vs. oxaliplatin. The results confirm that cisplatin activates JNK kinase 5.7 ± 1.5 (s.d.)-fold more efficiently in DNA mismatch repair-proficient than repair-deficient cells, and that the c-Abl response to cisplatin is completely absent in DNA mismatch repair-deficient cells. In contrast, there was no detectable activation of the JNK or c-Abl kinases in DNA mismatch repair-proficient or -deficient cells exposed to oxaliplatin. The present study demonstrates that, despite the similarity of the adducts produced by cisplatin and oxaliplatin, they appear to be recognized by different detectors. The DNA mismatch repair system plays an important part in the recognition of cisplatin adducts, and activation of both the JNK and c-Abl kinases in response to cisplatin damage is dependent on the detector function of the DNA mismatch repair proteins. In contrast, this detector does not respond to oxaliplatin adducts. © 1999 Cancer Research Campaig

Characterization and social correlates of fecal testosterone and cortisol excretion in wild male Saguinus mystax

Reproductive success in male primates can be influenced by testosterone (T) and cortisol (C). We examined them in wild Saguinus mystax via fecal hormone analysis. Firstly, we wanted to characterize male hormonal status over the course of the year. Further we tested the influence of the reproductive status of the breeding female, social instability, and intergroup encounter rates on T levels, comparing the results with predictions of the challenge hypothesis (Wingfield et al., 1990). We also tested for interindividual differences in hormonal levels, possibly related to social or breeding status. We collected data during a 12-mo study on 2 groups of moustached tamarins at the Estación Biológica Quebrada Blanco in northeastern Peru. We found fairly similar T and C levels over the course of the year for all males. Yet an elevation of T shortly after the birth of infants, during the phase of ovarian inactivity of the group’s breeding female, was evident. Hormonal levels were not significantly elevated during a phase of social instability, did not correlate with intergroup encounter rates, and did not differ between breeding and nonbreeding males. Our results confirm the challenge hypothesis (Wingfield et al., 1990). The data suggest that reproductive competition inmoustached tamarins is not based on endocrinological, but instead on behavioral mechanisms, possibly combined with sperm competition.Deutsche Forschungsgemeinschaft (HE 1870/10-1,2

A plesiosaur containing an ichthyosaur embryo as stomach contents from the Sundance Formation of the Bighorn Basin, Wyoming

Herein we report the discovery of an ichthyosaur embryo from the Upper Member of the Sundance Formation (Oxfordian) of the Bighorn Basin, Wyoming. The specimen is the first known ichthyosaur embryo from the Upper Jurassic, and is the first Jurassic ichthyosaur embryo from North America. The embryo was discovered in close association with the abdomen of an articulated partial plesiosaur skeleton, and several lines of evidence support the interpretation of the embryo as plesiosaur stomach contents. The small size and extremely poor ossification of the embryo indicate that the animal was probably not a neonate. Although the taxonomic affinities of the fossil are unknown, the large ichthyosaurian (sensu stricto) Opthalmosaurus natans is the only known ichthyosaur from the Sundance Formation, and the embryo may belong to that taxon

Female chacma baboons form strong, equitable, and enduring social bonds

Analyses of the pattern of associations, social interactions, coalitions, and aggression among chacma baboons (Papio hamadryas ursinus) in the Okavango Delta of Botswana over a 16-year period indicate that adult females form close, equitable, supportive, and enduring social relationships. They show strong and stable preferences for close kin, particularly their own mothers and daughters. Females also form strong attachments to unrelated females who are close to their own age and who are likely to be paternal half-sisters. Although absolute rates of aggression among kin are as high as rates of aggression among nonkin, females are more tolerant of close relatives than they are of others with whom they have comparable amounts of contact. These findings complement previous work which indicates that the strength of social bonds enhances the fitness of females in this population and support findings about the structure and function of social bonds in other primate groups