60 research outputs found

    Endocrine Active UV Filters: Developmental Toxicity and Exposure Through Breast Milk

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    Several UV filters exhibit endocrine activity. Evidence for transdermal passage and presence in the food chain (fish) suggests potential exposure of humans during development. Developmental toxicity was studied in rats for the estrogenic UV filters 4-methylbenzylidene camphor (4-MBC, 0.7, 7, 24, 47 mg/kg/day) and 3-benzylidene camphor (3-BC, 0.07, 0.24, 0.7, 2.4, 7 mg/kg/day) administered in chow to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. Neonates exhibited enhanced prostate growth after 4-MBC and altered uterine gene expression after both filters. 4-MBC and 3-BC delayed male puberty and affected reproductive organ weights of adult offspring. Interactions with the thyroid were noted. Expression and estrogen sensitivity of target genes and nuclear receptor coregulators were altered at mRNA and protein levels in adult uterus, prostate and brain. Female sexual behavior was affected by 4-MBC and 3-BC, estrous cycles by 3-BC. Classical endpoints exhibited LOAELs/NOAELs of 7/0.7 mg/kg/day for 4-MBC and 0.24/0.07 mg/kg/day for 3-BC. Molecular endpoints were affected by the lowest doses. In order to obtain information on human exposure, we conducted a monitoring study on human milk with three series of mother–child pairs (2004, 2005, 2006), with focus on cosmetic UV filters in relation to other endocrine disrupters. Methods for UV filter analysis followed the principles of European standardized methods for pesticide residue analysis (EN 15289). In cohorts 2004 and 2005, 78.8% of women reported use of product(s) containing cosmetic UV filters in a questionnaire, and 76.5% of milk samples contained these filters. Use of UV filters and concentration in human milk were significantly correlated. The results agree with the idea of transdermal passage of UV filters. They also indicate that it may be possible to reduce human exposure during critical periods such as pregnancy and lactation by transiently abstaining from use

    Differential cross sections for pion charge exchange on the proton at 27.5 MeV

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    We have measured pion single charge exchange differential cross sections on the proton at 27.5 MeV incident π\pi^- kinetic energy in the center of momentum angular range between 00^\circ and 5555^\circ. The extracted cross sections are compared with predictions of the standard pion-nucleon partial wave analysis and found to be in excellent agreement.Comment: ReVTeX v3.0 with aps.sty, 23 pages in e-print format, 7 PostScript Figures and 4 Tables, also available via anonymous ftp at ftp://helena.phys.virginia.edu/pub/preprints/scx.p

    Rhizobacterial salicylate production provokes headaches!

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    Manipulation of salicylate content in Arabidopsis thaliana by the expression of an engineered bacterial salicylate synthase.

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    Salicylic acid (SA) plays a central role as a signalling molecule involved in plant defense against microbial attack. Genetic manipulation of SA biosynthesis may therefore help to generate plants that are more disease-resistant. By fusing the two bacterial genes pchA and pchB from Pseudomonas aeruginosa, which encode isochorismate synthase and isochorismate pyruvate-lyase, respectively, we have engineered a novel hybrid enzyme with salicylate synthase (SAS) activity. The pchB-A fusion was expressed in Arabidopsis thaliana under the control of the constitutive cauliflower mosaic virus (CaMV) 35S promoter, with targeting of the gene product either to the cytosol (c-SAS plants) or to the chloroplast (p-SAS plants). In p-SAS plants, the amount of free and conjugated SA was increased more than 20-fold above wild type (WT) level, indicating that SAS is functional in Arabidopsis. P-SAS plants showed a strongly dwarfed phenotype and produced very few seeds. Dwarfism could be caused by the high SA levels per se or, perhaps more likely, by a depletion of the chorismate or isochorismate pools of the chloroplast. Targeting of SAS to the cytosol caused a slight increase in free SA and a significant threefold increase in conjugated SA, probably reflecting limited chorismate availability in this compartment. Although this modest increase in total SA content did not strongly induce the resistance marker PR-1, it resulted nevertheless in enhanced disease resistance towards a virulent isolate of Peronospora parasitica. Increased resistance of c-SAS lines was paralleled with reduced seed production. Taken together, these results illustrate that SAS is a potent tool for the manipulation of SA levels in plants

    Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

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    Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate <0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions
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