Cytotoxicity of TBBPA and effects on proliferation, cell cycle and MAPK pathways in mammalian cells

Poly-brominated flame retardants are ecotoxicologically relevant chemicals that can show high persistency in environmental samples and bioaccumulation in marine and fresh water animals. One of the most widely used compound is tetrabromobisphenol A (TBBPA). Until today, the toxicological data are rather fragmentary. Our studies on acute and sub-acute toxic effects with established cell lines demonstrate that TBBPA interferes with cellular signaling pathways. Cell viability is significantly reduced in a time- and concentration-dependent manner. The observed EC50 for rat kidney cells (NRK) was 52 microM (27 mg/l), 168 microM (90 mg/l) for A549 human lung cells, and 200 microM (108 mg/l) for Cal-62 human thyroid cells, respectively. The comparison of TBBPA with the non-brominated substance bisphenol A (BPA) clearly demonstrates that only the brominated compound exerts these effects on proliferation and cell viability. Cell cycle regulation was influenced considerably in Cal-62 cells, showing an explicit G2/M arrest in the cell cycle at TBBPA concentrations higher than 75 microM. Cellular signaling pathways directly connected to these affected parameters, e.g. the mitogen activated protein kinase (MAPK) cascades, are partly influenced in a cell specific and dose dependent manner. The extracellular-signal regulated kinase (ERK) is deactivated in NRK and A549 cells and activated in Cal-62 cells with increasing TBBPA concentrations.     

(−)-Acetylcarnitin und Succinatoxydation

The Science of Nature -     

Evaluating the influence of nature connection and values on conservation attitudes at a tropical deforestation frontier

Inner phenomena, such as personal motivations for pursuing sustainability, may be critical levers for improving conservation outcomes. Most conservation research and policies, however, focus on external phenomena (e.g., ecological change or economic processes). We explored the factors shaping 9 conservation attitudes toward forest and wildlife protection among colonist farmers around an Amazonian deforestation frontier. Our data comprised 241 face-to-face quantitative surveys, complemented with qualitative insights from open-ended questionnaire responses and opportunistic semistructured interviews. To account for the full spectrum of possible inner motivations, we employed measures of nature connection (indicating biospheric motivation) and personal values organized around the traditionalism (traditionalist through to high openness to change) and universalism dimensions (egoistic through to altruistic motivations). We used averaged beta-binomial generalized linear models to assess the role of external factors (socioeconomic, sociodemographic, and environmental) and personal (inner) motivations on the variation in attitudes. Each attitude was modeled separately. The relative importance of each predictor was judged by the proportion of models where it appeared as significant. Proconservation views were expressed by the majority (at least 65%) of the respondents in 7 out of the 9 attitude models. The most consistent predictors were emotional nature connection and personal values (significant in 4–6 out of 9 models), rather than external phenomena (significant in 0–5 models). However, the poorest farmers had lower scores on the agreement with prioritizing nature over development (𝛽 = –0.52, 95% CI: –0.96 to –0.07). Qualitative data also indicated that economic barriers hinder forest conservation on farms. These results suggest that biospheric, traditionalistic, and altruistic motivations promote people's proconservation attitudes, but nurturing these latent motivations is unlikely to improve conservation outcomes if material poverty remains unaddressed. Integrating the inner–outer perspective into conservation thinking and practical interventions could foster environmental stewardship and increase human well-being.     

Tissue free water tritium and organically bound tritium in the rice plant acutely exposed to atmospheric HTO vapor under semi-outdoor conditions.

Potted rice plants were exposed to atmospheric HTO in a box outdoors for 1 h at 9 different times from booting to yellow-ripe stages. It is indicated that the leaf TFWT concentration may reach equilibrium within 1 h in clear weather. The plant TFWT concentration decreased at a rapid rate for the first several hours and at a much slower rate thereafter. The decrease till harvest was by factors of 600-95,000 depending on the plant parts and exposure times. The time course of the ear OBT concentration was characterized by the exposure time. After exposure at the booting to heading stages, the leaf OBT concentration decreased rapidly for the first several hours and then very slowly. The plant OBT concentration was initially about 2 orders of magnitude lower, but at harvest an order of magnitude higher, than the TFWT concentration. The OBT concentration in hulled seeds at harvest varied with exposure times by a factor of 70, being highest in the exposure performed at the earlier stage of rapid grain growth. Also in this exposure, the plant total OBT was greatest due to the seed OBT.     

A technical mixture of 2,2',4,4'-tetrabromo diphenyl ether (BDE47) and brominated furans triggers aryl hydrocarbon receptor (AhR) mediated gene expression and toxicity

Polybrominated diphenyl ethers (PBDE) are found as ubiquitous contaminants in the environment, e.g., in sediments and biota as well as in human blood samples and mother's milk. PBDEs are neuro- and developmental toxins, disturb the endocrine system and some are even carcinogenic. Structural similarities of PBDEs with dioxin-like compounds, e.g., 2,3,7,8-tetrachloro-dibenzodioxin (TCDD), have raised concern about a possible "dioxin-like" action of PBDEs. TCDD exerts its toxicity via binding to and activation of the aryl hydrocarbon receptor (AhR). AhR ligands are in contrast to PBDEs usually coplanar compounds. Thus, PBDEs are not likely to be strong AhR agonists. The aim of this study was to analyze the effects of the most abundant PBDE congener, 2,2',4,4'-tetrabromo diphenyl ether (BDE47), on AhR activity and signaling. Initially, we measured cytochrome P450 1A1 (Cyp1A1) induction as a readout for AhR activation by BDE47. Low grade purified BDE47 increased CYP1A1 levels in transformed and primary rat hepatocytes and human hepatoma cells. Chemical analysis of the BDE47 sample identified trace contaminations with brominated furans such as 2,3,7,8-tetrabromo dibenzodioxin (TBDF), which most likely were responsible for the observed activation of AhR. Subsequently, the BDE47 mixture was studied for its effect on AhR mediated toxicity and global gene expression. Indeed, in rat hepatoma cells and in zebrafish embryos the BDE47 mixture provoked changes in gene expression and toxicity similar to known AhR agonists. In addition to the dioxin-like actions, the BDE47 sample enhanced Cyp2B and Cyp3A expression suggesting that commercial PBDE mixtures, which also often contain brominated furans, may disturb cellular homeostasis at multiple levels.