Mixtures of Chemicals in Water: Implications of chemical legislation and environmental policy

Scientists have shown that mixtures of chemicals can act together to reduce the reproductive capacity of fish even if each individual chemical in the mixture is present at a concentration that does not cause an adverse effect. This evidence demonstrates that legislation based on the assessment of single chemicals may not be sufficiently protective and suggest that there is a need for a review of existing environmental policy

Preliminary data on the influence of rearing temperature on the growth and reproductive status of fathead minnows Pimephales promelas

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2011 Brian JV et al.An investigation into the influence of temperature on the growth and reproductive status of the fathead minnow Pimephales promelas revealed that, while there was no clear effect of treatment on sex differentiation, ovarian tissue from female fish reared under the highest temperature regime contained large amounts of undefined tissue containing no germ cells. Furthermore, both male and female fish exhibited differences in length mass, condition and somatic indices, and in the expression of secondary sexual characteristics. The patterns observed are discussed in the context of climate change

Benzotriazole is antiestrogenic in vitro but not in vivo

Copyright © 2007 SETAC. This is the accepted version of the following article: Harris et al (2007), "Benzotriazole is antiestrogenic in vitro but not in vivo", Environmental Toxicology and Chemistry, 26(11), 2367–2372, which has been published in final form at the link below.Benzotriazole (BT) is an anticorrosive agent well known for its use in aircraft deicing and antifreeze fluids but also used in dishwasher detergents. It is highly persistent in the environment; therefore, BT is frequently found in runoff emanating from large airports as well as in the surrounding groundwater. In addition, BT has recently been found to be ubiquitous in Swiss wastewater treatment plant effluents and their receiving waters; however, very little chronic toxicity data is available on which to base a sound ecological risk assessment of this chemical. In vitro assays conducted using a recombinant yeast (anti-) estrogen assay indicated that BT possessed clear antiestrogenic properties. This chemical was approximately 100-fold less potent than Tamoxifen, which was used as a positive control. A subsequent in vivo study, however, involving analysis of vitellogenin induction and somatic indices in adult fathead minnows (Pimephales promelas) exposed to BT at concentrations of 10, 100, and 1,000 μg/L for two weeks showed no evidence of antiestrogenic activity by this compound. The possibility exists that higher concentrations of BT may yet induce the type of activity observed in vitro, although the concentrations used here already far exceed those reported in surface-water samples. Furthermore, adverse effects may be observed in fish or other organisms exposed to BT for a longer period than employed here, although such studies are costly and unlikely to be included in standard risk assessment procedures. A rigorous investigation of the chronic toxicity of BT is imperative

Histone modifiers are oxygen sensors.

Hypoxia signals directly to chromatin via histone demethylases to alter gene expression</jats:p

Prognostic models turn the Heat(IT)up on FLT3ITD-mutated AML.

The presence of internal tandem duplications (ITDs) in the FLT3 receptor tyrosine kinase gene have long been known to confer a poor prognosis to acute myeloid leukemia (AML) patients. Now, specific structural features of the ITD are also suggested to alter patient outcome, including sensitivity to targeted therapies, prompting their evaluation in therapeutic algorithms.B.J.P. Huntly is supported by The European Research Council (COMAL: 647685) and Cancer Research UK (A25508). P. Gallipoli is supported by the Wellcome Trust (109967/Z/15/Z) and an ASH Global Research Award

Hypoxia does not influence the response of fish to a mixture of estrogenic chemicals

The official published version can be obtained from the link below - Copyright @ 2009 American Chemical SocietyChemical risk assessment procedures assign a major role to standardized toxicity tests, in which the response of a particular organism to a single test substance is determined under otherwise constant and favorable conditions in the laboratory. This approach fails to consider the potential for chemical interactions, as well as failing to consider how the toxicological response varies, depending on the conditions of exposure. As yet, the issue of confounding factors on chemically mediated effects in wildlife has received little attention, despite the fact that a range of physicochemical parameters, including temperature, water quality, and pH, are known to modify chemical toxicity. Here, we consider how the estrogenic response of fish varies with regard to hypoxia. Fathead minnows (Pimephales promelas) were exposed to a mixture of estrogenic chemicals under hypoxic or normoxic conditions. Their estrogenic response was characterized using an in vivo assay, involving the analysis of the egg yolk protein, vitellogenin (VTG). The results revealed that there was no effect of hypoxia on the VTG response in either treatment group at the end of the exposure period. This suggests that this end point is robust and relatively insensitive to the effects of any physiological changes that arise as a result of hypoxia. The implications of these negative findings are discussed in terms of their relevance with regard to the development of risk assessment policy.This work was funded by a grant from the Natural Environment Research Council(NE/D00389X/1)

The influence of a surfactant, linear alkylbenzene sulfonate, on the estrogenic response to a mixture of (xeno)estrogens in vitro and in vivo

This is the post-print version of the final paper published in Aquatic Toxicology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright © 2008 Elsevier B.V. All rights reserved.The effect of the presence of a surfactant on the activity of a mixture of environmental estrogens was assessed. In their natural habitat, fish are subject not only to exposure to mixtures of estrogenic compounds, as has been addressed in previous publications, but also to other confounding factors (chemical, physical and biological), which may, in theory, affect their responses to such compounds. To assess the potential for such interference, the commonly occurring surfactant, linear alkylbenzene sulfonate (LAS), was applied to the yeast estrogen screen at various concentrations, independently and together with a mixture of estrogens at constant concentrations. LAS enhanced the estrogenic activity of the mixture, an effect which became less pronounced over the course of time. This information was used to design an in vivo study to assess induction of vitellogenin in fathead minnows exposed to the same mixture of estrogens plus LAS. A similar trend was observed, that is, the response was enhanced, but the effect became less pronounced as the study progressed. However, the enhanced response in vivo occurred only at the highest concentration of LAS tested (362 μg/L), and was transient because it was no longer apparent by the end of the study. Although LAS is a significant contaminant in terms of both concentration and frequency of detection in the aquatic environment, these data do not suggest that it will have a significant impact on the response of fish to environmental estrogens

Acute myeloid leukemia: leukemia stem cells write a prognostic signature

In a recent interesting article, analysis of gene expression between phenotypically defined acute myeloid leukemia (AML) leukemia stem cells (LSCs) and more mature leukemia progenitor cells is used to generate a differentially expressed gene signature for LSCs. Through clever bioinformatic weighting analysis, the authors describe a method to convert this signature into a single score for any given sample and then test the prognostic utility of this 'LSC score' in publicly available gene expression profiles from bulk AML samples. They demonstrate that a high LSC score is associated with poor prognosis in AML patients and further demonstrate that the score is independent of known prognostic factors, including age, karyotype and mutation of the FLT3 or NPM1 genes. These findings are important and directly relate transcriptional dysregulation in AML LSCs with the outcome in patient samples, thus reinforcing the belief that these cellular populations are crucial for the initial propagation and subsequent relapse and resistance of leukemia