The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

Background: This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders.

No abstract

Flanders, Belgium, is one of the most densely populated areas in Europe. The Flemish Environment and Health Survey (2002-2006) aimed at determining exposure to pollutants of neonates, adolescents, and older adults and to assess associated biological and health effects. This study investigated genome wide gene expression changes associated with a range of environmental pollutants, including cadmium, lead, PCBs, dioxin, hexachlorobenzene, p,p'-DDE, benzene, and PAHs. Gene expression levels were measured in peripheral blood cells of 20 adults with relatively high and 20 adults with relatively low combined internal exposure levels, all non-smokers aged 50-65. Pearson correlation was used to analyze associations between pollutants and gene expression levels, separately for both genders. Pollutant- and gender-specific correlation analysis results were obtained. For organochlorine pollutants, analysis within genders revealed that genes were predominantly regulated in opposite directions in males and females. Significantly modulated pathways were found to be associated with each of the exposure biomarkers measured. Pathways and/or genes related to estrogen and STAT5 signaling were correlated to organochlorine exposures in both genders. Our work demonstrates that gene expression in peripheral blood is influenced by environmental pollutants. In particular, gender-specific changes are associated with organochlorine pollutants, including gender-specific modulation of endocrine related pathways and genes. These pathways and genes have previously been linked to endocrine disruption related disorders, which in turn have been associated with organochlorine exposure. Based on our results, we recommend that males and females be considered separately when analyzing gene expression changes associated with exposures that may include chemicals with endocrine disrupting properties.