Toxicoproteomics – The Next Step in the Evolution of Environmental Biomarkers?

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Toxicological Sciences





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The scientific community has become increasingly concerned about the potential adverse health effects to humans and wildlife resulting from environmental exposure to persistent industrial, pharmaceutical, and natural chemicals with estrogenic, androgenic, or thyroid-disrupting properties (Colborn et al., 1993; Waring and Harris, 2005). To assess exposure to these endocrine-disrupting chemicals (EDCs), researchers have employed a variety of molecular biomarkers. A high-quality biomarker of a specific chemical class or specific mechanism of action should have the following attributes: (1) the biomarker should be inducible or repressible, (2) the measured response should be specific to chemicals within that class, (3) the response should have sufficient sensitivity for routine detection, (4) the biomarker should be highly accurate and reproducible among experiments within a laboratory and among different laboratories and animal models, and (5) the biomarker should be quantifiable so that degree of risk can be estimated. One of the most utilized biomarkers of EDC exposure is the egg yolk precursor protein vitellogenin (Vtg), which is highly expressed in the liver and plasma of oviparous animals in response to 17β-estradiol. Induction of plasma Vtg in fish has been routinely used as a biomarker of xenoestrogen exposure, both in controlled laboratory settings and in field studies (Sumpter and Jobling, 1995), and is currently being incorporated as a standard tier 1 bioassay within the U.S. Environmental Protection Agency Endocrine Disruptor Screening Program. Other examples of biomarkers of estrogenicity include in vitro assessment of MCF-7 cell proliferation, estrogen receptor binding and transactivation, and in vivo assessment of endometrial thickness in mammals.