title: High intake of dietary sugar enhances bisphenol A (BPA) disruption and reveals ribosome-mediated pathways of toxicity.
abstract: Bisphenol A (BPA) is an organic compound to which human populations are ubiquitously exposed. Epidemiological data suggest BPA exposure might be associated with higher rates of diabetes and reproductive anomalies. Health concerns also include transgenerational consequences, but these mechanisms are crudely defined. Similarly, little is known about synergistic interactions between BPA and other substances. Here we show that acute and chronic exposure to BPA causes genome-wide modulation of several functionally coherent genetic pathways in the fruit fly Drosophila melanogaster. In particular, BPA exposure causes massive downregulation of testis-specific genes and upregulation of ribosome-associated genes widely expressed across tissues. In addition, it causes the modulation of transposable elements that are specific to the ribosomal DNA loci, suggesting that nucleolar stress might contribute to BPA toxicity. The upregulation of ribosome-associated genes and the impairment of testis-specific gene expression are significantly enhanced upon BPA exposure with a high-sugar diet. Our results suggest that BPA and dietary sugar might functionally interact, with consequences to regulatory programs in both reproductive and somatic tissues.
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115-6021.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Branco
authors.forename: Bernardo
authors.initials: B
authors.lastname: Lemos
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002466:Cell Nucleolus / Q000187:drug effects / Q000235:genetics; D019422:Dietary Sucrose / Q000009:adverse effects*; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D010636:Phenols / Q000633:toxicity*; D012270:Ribosomes / Q000187:drug effects* / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D019422:Dietary Sucrose; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; diabetes; nucleolus; ribosome; testis