S. Government. “
“Endocrine disruptors are described as exogenous substances that alter functions of the endocrine
system and consequently cause adverse health effects in organisms and/or their progeny (Damstra et al., 2002). A growing list of substances are now suspected of such endocrine disrupting properties, including industrial chemicals, such as polycyclic aromatic hydrocarbons (PAHs) (Arcaro et al., 1999), dioxins (Department of Health and Human Services Centers for Disease Control and Prevention, 2005), brominated flame find more retardants (Birnbaum and Staskal, 2004), several pesticides (Bretveld et al., 2007), bisphenol A (Maffini et al., 2006), phthalates (Lottrup et al., 2006), parabens (Harvey and Darbre, 2004), organic solvents (Luderer et al., 2004), and some metals (Queiroz and Waissmann, 2006), as well as the naturally occurring phytoestrogens
(North and Golding, 2000). Exposure to these substances occurs in everyday life and involves very different sources, such as diet, personal care products, tobacco smoke, and exposures at the workplace. Endocrine disruptors may interfere with the endocrine system through activating or blocking hormone A 1210477 receptors, but they can also alter the synthesis, metabolism, and clearance of endogenous hormones and thereby influence hormone bioavailability (Damstra et al., 2002). Endocrine disruptors are hypothesized to play a role in the pathogenesis of various disorders, including urogenital birth defects, endometriosis, male and female subfertility, and malignancies (Skakkebaek et al., 2001, Heilier et al., 2005, Hess-Wilson and Knudsen, 2006 and Darbre, 2006). However, epidemiological evidence PD184352 (CI-1040) for health risks of current exposure levels is scarce. In the past few years, a number of receptor-based assays have been developed that offer new possibilities for epidemiologic research into endocrine disruption, among which the Chemically
Activated LUciferase gene eXpression (CALUX®) bioassays (Murk et al., 1997 and Sonneveld et al., 2005). CALUX® bioassays constitute of a genetically modified cell line in which specific receptor responsive DNA elements are linked to a so-called reporter gene that transcribes to the easily measurable firefly (Photinus pyralis) protein luciferase. In essence, CALUX® bioassays measure receptor induced gene expression, which gives information about the expected biological response to chemicals in humans. For example, elevated or reduced gene expression measured with a CALUX® bioassay indicates whether specific substances would exert agonistic or antagonistic effects on the target cell level. In epidemiological investigations, CALUX® technology has mostly been used to assess internal exposure to dioxin-like substances (Pauwels et al., 2001, Den Hond et al., 2002, Nawrot et al., 2002, Koppen et al., 2002, Van Den Heuvel et al.