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Biomarkers and monitoring studies

See the following introductory video:

https://www.youtube.com/watch?v=eyWTiy5kva8&list=PLg5Y3I3CS1Tuxj-tyIKkxPdNITIGHZKz9&index=12


Measures of exposure, effect and susceptibility may be quantified at a variety of biological organization levels (molecular, cellular, organs system, organism, etc.). The term biomarker has been generally used to refer to a xenobiotically induced variation in cellular, or biochemical components as well as processes, structures, or functions that are measurable in a biological system or samples, resulting in a change in a normal status. This definition includes biochemical, physiological, histological, morphological, and behavioural measures.

Molecular biomarkers are typically indicators of exposure, effect or susceptibility.

Biomarkers do not directly provide information concerning impacts on the higher levels of organization considered in ecotoxicology. Nevertheless, biomarkers often provide important tools for discerning contaminant exposures and potential impacts of ecological relevance, as well as sensitive early warning signals or incipient ecological damage. Hence, biomarkers play an important role in monitoring studies in the evaluation of the effectiveness of remedial action of xenobiotic effects, to assess the quality of the environment and how it changes over time. Commonly, population level effects are referred to as "bioindicator" responses and changes at the community and ecosystem level are categorized as "ecological indicators".

Monitoring studies include chemical (soil, air, sediments and water) and biological (bioaccumulation or physiological response modification) approaches. In fact, some organisms present in the ecosystem may give the first signal of environmental contamination, called sentinel species.

The development and use of biomarkers in ecotoxicology appears as beneficial for many contaminants that show inherent instabilities, which make measures of exposure by direct tissue residue analysis difficult to perform. Moreover, the sensitivity and specificity of some biomarkers contribute to the identification of chemicals having biological effects and to assess the mechanisms of toxic action.

Van der Oost et al. (2003) have proposed six criteria for the evaluation of new biomarkers. According to these, a completely validated biomarker should fulfill all these criteria:

- reliable, cheap and easy to perform;

- sensitive to pollutants;

- defined baseline levels and known response to natural variations and toxic exposure;

- established response to confounding factors;

- known toxic mechanisms;

- established relationship between biomarker alterations and effects at higher biological levels.


Additional information can be found in the following article:

martinez-haro 2015


RNA content

The RNA content of an organism can be used as both fitness and toxicological endpoint. In addition to direct damaging effects and loss of protein functions resulting from exposure, xenobiotics may induce a number of protective proteins for both repair and detoxifying mechanisms, resulting in an increase of the DNA expression and hence, the RNA content. As the majority of the cellular RNA is ribosomal RNA (rRNA), which is correlated with the protein synthesis activity, the organismal RNA content is an indirect measurement of protein production associated to xenobiotic exposure effects.


Gene expression of specific proteins

In response to stress and adverse effects, the regulation of expression and transcription of specific genes may be altered. These responses are of primarily importance to understand the mode of action of the compounds. Considering the continuous increasing number of mapped genomes, particularly for model organisms, ecotoxicogenomics reveals a powerful tool to detect and identify these genotoxic effects. Microarrays are widely used for screening of genes expression alterations in response to stressors as multiple genes can be simultaneously assayed, providing information about up- and down- regulation of genes and limited quantitative information. Moreover, real-time qPCR technique gives full quantitative information of the gene expression changes for a specific gene.


Antioxidative defense

As it is difficult to measure the cellular concentration of short-lived Reactive Oxygen Species (ROS), induction of the antioxidative defense is used as a measure of enhanced ROS production, taking into account the activity of individual antioxidative enzymes like catalase (CAT), superoxide dismutase (SOD), gluthatione S-transferase (GST), etc. (Figure 5). However, it may be complicated to quantify and interpret the integrated response of the antioxidative defense system with this approach as individual enzymes can respond differently catalyzing specific reactions in the detoxification chain of ROS.

A
B

Figure 5 (A and B) - Oxidative stress and antioxidant defense.
Sources: http://pubs.sciepub.com/ajssm/1/1/2/image/fig1.gif; http://www.hindawi.com/journals/bmri/2014/831841.fig.001.jpg

When the balance of ROS production and antioxidative defense is disrupted, ROS adversely react with a variety of biomolecules such as lipids or proteins. Lipid peroxidation occurs as a result of ROS interactions and can often be measured by assaying their end-products, of which the most commonly assayed marker is malonic dialdehyde (MDA). This lipid damage may causes DNA adducts and damages on membrane associated proteins that alter the fluidity property of membranes.


REFERENCES

Derelanko MJ, Hollinger MA. (2001). Handbook of toxicology. 2nd edition. CRC Press LLC, Boca Raton, Florida. 1380p.

Hodgson E. (2010). A textbook of modern toxicology. 4th edition. John Wiley & Sons, Inc., Hoboken, New Jersey. 648p.

Klaassen CD. (2008). Casarett and Doull's Toxicology. The Basic Science of Poisons. 8th edition. McGraw-Hill Education, LLC, New York, USA. 1454p.

McQueen CA. (2010). Comprehensive Toxicology. 2nd edition. Elsevier Science. 7700p.

Robinson L, Thorn I. (2005). Toxicology and ecotoxicology in chemical safety assessment. Blackwell Publishing Ltd., Oxford, UK. 157p.

Van der Oost R, Beyer J, Vermeulen NPE (2003). Fish bioaccumulation and biomarkers in environmental risk assessment: a review. Environmental Toxicology and Pharmacology 13(2): 57- 149.


Online resources

http://www.aces.su.se/itm/documents/publications/lic_kappa_sarafuruhagen.pdf

http://tmedweb.tulane.edu/pharmwiki/doku.php/drug_receptor_theory

http://pubs.sciepub.com/ajssm/1/1/2/image/fig1.gif

OECD Guidelines: http://www.oecd.org/env/ehs/testing/TG_List_EN_Jul_2013.pdf

EPA Guidelines: http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm