Biomarkers integrated approach

In 2004, Melle et al.12 proposed a technical triad of microdissection, pro-teomic techniques, and IHC that provides an integrated approach for characterization of cancer biomarkers. In recent years, a growing body of literature pertaining to this combined approach has accumulated. Table 22.1 shows a few selected examples under this topic. 

Ball, G., Mian, S., Holding, R, Allibone, R.O., Lowe, J., Ali, S., Li, G., McCardle, S., Ellis, I.O., Creaser, C., and Rees, R.C., An integrated approach utilizing neural networks and SELDI mass spectrometry for classification of human tumours and rapid identification of potential biomarkers. Bioinformatics, 18, 395 04, 2002. 

Martfn-Dfaz ML, Villena-Lincoln A, Bamber S, Blasco J, DelValls TA. 2005b. An integrated approach using bioaccumulation and biomarker measurements in female shore crab, Carcinus maenas. Chemosphere 58 615-626. 

Plata-Salaman, C. R. (2004). Biomarker discovery and validation technologies and integrative approaches. Trends Biotechnol. 22,411-416. 

The aim of this chapter is to show how biomarkers can be used as simple, rapid cost-effective techniques to aid in an integrated approach to environmental management and risk assessment. Specifically, we use the Fal and Helford Estuaries located in the south west of England as a case study to highlight the application of biomarkers and to illustrate how they can aid ERA. 

SHARED MECHANISM OF ACTION—AN INTEGRATED BIOMARKER APPROACH TO MEASURING THE TOXICITY OF MIXTURES... 

In a similar way, an integrated biomarker approach has a role when carrying out experiments in mesocosms. Under these controlled conditions, behavioral effects of neurotoxic pollutants, acting singly or in combination, can be monitored and compared with data on predator-prey relationships and effects at the population level. The employment of mechanistic biomarker assays can facilitate comparisons between results obtained in mesocosms and other data obtained in the field or in laboratory tests. Here is one way of attempting to answer the difficult question— how comparable are mesocosms to the real world ... 

NOMIRACLE (2004-2009, http //viso.jrc.it/nomiracle/) provided support to the development and improvement of a coherent series of methodologies underpinned by mechanistic understanding, while integrating the risk analysis approaches of environmental and human health. The project delivered understanding of and tools for sound risk assessment, developing a research framework for the description and interpretation of combined stressor effects that leads to the identification of biomarkers and other indicators of cumulative impacts. 

It is noteworthy that the styrene reference concentration (RfC) in the Integrated Risk Information System is based on the biomarker-response relationship found in workers (Mutti et al. 1984 EPA 1998). The Environmental Protection Agency (EPA) used the relationship of urinary biomarker to ambient-air concentration of workers to develop an RfC that was adjusted for the difference in exposure time between the workplace and the general population. That is a valid approach because it derives a workplace concentration-toxicity relationship in workers, which can then be adjusted for the general population to account for differences in exposure time and can take uncertainty factors into account. It is different from direct adjustment of the styrene BEI to evaluate human population biomonitoring data on styrene metabolites in urine, which would have the uncertainties described above and in Chapter 5. 

Yunker, M.B., Macdonald, R.W., Veltkamp, D.J., and Cretney, W.J. (1995) Terrestrial and marine biomarkers in a seasonally ice-covered Arctic estuary—integration of multivariate and biomarker approaches. Mar. Chem. 49, 1-50. 

Perhaps the most important argument to use such biomarker approaches lies in their inherent potential to integrate the exposure to compounds that are hitherto unknown or unidentified and to account for interactions like synergism or antagonism. 

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