Biomarkers susceptibility

Animal-to-Human Extrapolations ENDOCRINE DISRUPTION CHILDREN S SUSCEPTIBILITY BIOMARKERS OF EXPOSURE AND EFFECT... 

Extensive research is currently underway to use biological markers (biomarkers) in exposure and risk assessment. Biomarkers include the reaction products of chemicals or their metabolic products with biological macromolecules, especially with DNA. They also involve indicators of effect, such as chromosomal damage, and indicators of individual genetic susceptibility. 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism s ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are discussed in Section 3.10 Populations That Are Unusually Susceptible. 

Experimental evidence in humans is based upon intervention studies with diets enriched in carotenoids or carotenoid-contaiifing foods. Oxidative stress biomarkers are measured in plasma or urine. The inhibition of low density lipoprotein (LDL) oxidation has been posmlated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Since carotenoids are transported mainly via LDL in blood, testing the susceptibility of carotenoid-loaded LDL to oxidation is a common method of evaluating the antioxidant activities of carotenoids in vivo. This type of smdy is more precisely of the ex vivo type because LDLs are extracted from plasma in order to be tested in vitro for oxidative sensitivity after the subjects are given a special diet. 

Subcategories of bioindicators at suboiganismal levels are generally referred to as biomarkers. Biomarkers may reflect either exposure, effect, or susceptibility of these, biomarkers of effect are both more valuable and more difficult to find. An ideal biomarker of mercury effect would be ... 

Cavalieri, E. Chakravarti, D. Guttenplan, J. Hart, E. Ingle, J. Jankowiak, R. Muti, P Rogan, E. Russo, J. Santen, R. Sutter, T. Catechol estrogen quinones as initiators of breast and other human cancers implications for biomarkers of susceptibility and cancer prevention. Biochim. Biophys. Acta 2006, 1766, 63-78. 

Kavanaugh TJ University of Washington, Seattle, WA Glutathione regulation as a biomarker of exposure to toxicants and of susceptibility to such exposures National Institute of Environmental Health Sciences... 

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