Response biomarkers

In view of these complexities, environmental studies that seek to verify proposed cause-effect relationships between contamination and response need to be carefully designed to avoid bias and misunderstanding. Most environmental assessments adopt a multi-tiered approach to testing, in which combinations of biological responses (biomarkers) are measured in tissue samples, body fluids or at the whole organism level to indicate exposure to or adverse effects of contamination.8. Auffret and colleagues60 surveyed Pacific oysters from the Atlantic coast of Brittany after the Erika oil spill between... 

Parrott, J.L. and Tillitt, D.E. 1997,The use of Semipermeable Membrane Devices (SPMDs) to Concentrate Inducers of Fish Hepatic Mixed Function Oxygenase (MFO). In Ecotoxicology Responses, Biomarkers, and Risk Assessment. An OECD Workshop Zelikoff, J.T., Ed. SOS Publications Pair Haven, NJ. pp. 185—196. 

Prediction of responses Biomarker to individual DEB approaches 4 Extrapolation across 4.2.2... 

Known, not novel, dose-responsive biomarkers present in two relevant toxicology species Known, exaggerated pharmacology Single, escalating-dose in healthy subjects No AEs observed at any dose levels No NOEL determined in either species 5 mg/kg in mouse and monkey... 

Poorly understood, dose-responsive biomarkers in 1 toxicology species Poorly understood, monitorable Repeat, escalating dose in end stage disease population... 

Zeeman M (1997) Aquatic toxicology and ecological risk assessment US-EPA/OPPT perspective and OECD interactions. In Zelikoff JT, Lynch J, Schepers J (eds) Ecotoxicology Responses, Biomarkers, and Risk Assessment. Organization for Economic Cooperation Development, Paris, pubhshed for the OECD by SOS Publications, Pair Haven, N.J., pp 89-108... 

Stigson M, Kultima K, Jergil M, et al. Molecular targets and early response biomarkers for the prediction of developmental toxicity in vitro. Altern Lab Anim. 2007 35(3) 335-342. 

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. Biomarkers of susceptibility are discussed in Section 6.10, Populations That Are Unusually Susceptible. 

Stiirzenbaum, S.R., Kille, P. and Morgan, A.J. (1998b) Identification of new heavy-metal-responsive biomarker in the earthworm. In Advances in Earthworm Ecotoxicology, Sheppard, S.C., Bembridge, J.D., Holmstmp, M. and Posthuma, L. (eds), pp. 215-224. SETAC, Pensacola, EL. 

Bols, N.C., J.J. Whyte, J.H. Clemons, DJ. Tom, M. van den Heuvel and D.G. Dixon. Use of liver cell lines to develop toxic equivalency factors and to derive toxic equivalent concentrations in environmental samples. In Ecotoxicology Responses, Biomarkers and Risk Assessment, edited by J.T. Zelikoff, Fair Haven, NJ, SOS Publications, pp. 329-350, 1997. 

Sweet, L.I., D.R. Passino-Reader, P.G. Meier and G.M. Omann. Xenobiotic-induced apoptosis significance and potential application as a general biomarker of response. Biomarkers 4 237-253, 1999. 

All the values allowing an accurate evaluation of the endpoints (toxicity and clinical response biomarkers, surrogate endpoints, or clinical endpoints). Treatment data, for example, dose and actual times of start and end of infusion. 

J. K. Frederickson and H. Bolton, Jr., Terrestrial Microcosms for risk Assessment of Soil-Applied Microorganisms and Pesticides , in J. T. SelikofFs, Ed., Ecotoxicology Responses, Biomarkers and Risk Assessment, Organization for Economic Co-operation and Development, Paris, 1997, pp. 459-488. 

Each section of this chapter is divided into the biomarker compound class (i.e., nucleic acids, proteins, and lipids) and further divided into endogenous biomarkers, which are typically formed by direct oxidative action on the compound, or response biomarkers, which may be a combination thereof. For example, when smokers are compared with nonsmokers, there is inereased ROS-mediated formation. In addition, there is also inereased lipid hydroperoxide-mediated DNA damage resulting in the formation of HedGuo. The results from the numerous studies deseribed in this ehapter are meant to give an overview of the accomplishments within the years 2005 2009. Thus, this chapter is not intended to be comprehensive. 

LC—MS has provided researchers an invaluable tool to analyze oxidative metabolites and adducts on lipids, nucleic acids, and proteins. Many of these oxidative metabolites go on to form adducts such as the HedGuo from ONE and 1-iV -propano-dGuo from ACR. For the most part, these modifications are used as individual biomarkers of specific disease states. Only recently has there been an emphasis on the formation of a panel of biomarkers for specific disease states or environmental exposures. For instance, our laboratory has focused on exposure and response biomarkers of cigarette smoke. Many of these reactive compounds have been implicated in cancers, pulmonary diseases, and cardiovascular diseases, to name a few. A panel of biomarkers that range from oxidized DNA adducts to IsoPs has provided a tool to better understand different patterns of disease progression and biological outcomes. 

Milk Fat Inhibits Growth and Modulates CLA-Responsive Biomarkers in MCF-7 and SW480 Human Cancer Cell Lines, 90 877—885 (2003). 

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