I.

Biomarkers:
1) Definition:
A biomarker defined as "any biological response to an environmental product observed at a level below
that of the individual".
For example, it is a biological response to a chemical element (pesticides, PAHs, metal, etc.) which
induces stress and which allows exposure to a toxic substance to be shown "(Wocks, 1995).
oxidative stress or oxidative stress corresponds to an attack on cells by free medics, also called "reactive
oxygen species" (ROS). Oxidative stress, which is observed at the cellular level, and stress should not be
confused. psychological, at the level of the organism.
Therefore, a biomarker is an observable and / or measurable change at the molecular, biochemical,
cellular, physiological or behavioral level, which reveals the exposure present (persistent) or passed from
an individual to at least one chemical substance of a polluting nature (Lagadie et al, 1997).
Biomarkers are measured in organisms exposed to stress conditions linked to the presence of polluting
substances in the environment.
They represent the initial biological response of organisms to disturbances or contaminations of the
environment in which they live.
The inhibition or induction of biomarkers are good ecotoxicological tools for evaluating exposure and
evaluating the potential effects of xenobiotics on the organism.
Example:
a) Blood cholinesterase are inhibited by organophosphate or carbamate insecticides at very low doses.
b) The anminolevulinate dehydratase (ALAD) activity is inhibited by lead (Rivière, 1998).
c) Cytochrome P450 enzymes in the liver or other tissues (lungs) involved in the degradation of
xenobiotics are induced by numerous organic pollutants: PAHs, PCBs, dioxins (Roos, 1996;
Fouchécouri, 1996), they normally lead to easier elimination of metabolites, while for other toxicants,
biotransformation result in reactive metabolites that are sometimes more toxic than the parent
molecules. It is now recognized that the increase in the level of cytochrome P450 in fish can be used
as an indicator of environmental contamination or as an early indicator of the alteration of the biology
of organisms exposed to chemical pollutants.
2). Types of biomarkers:
Classically, the authors (Lagadie et al., 1997; Kammenga et al., 2000) distinguish biomarkers into
exposure biomarkers, effect biomarkers and sensitivity biomarkers.
 Biomarkers of exposure:
Biomarkers of exposure are induced by a specific type of pollutant and, therefore, their variations
are indicative of the body's exposure to that class of pollutants. These biomarkers are said to be
specific, such as enzymes which are biomarkers of neurotoxicity.
 Biomarker intervention process: see the figure
A. Organic pollutants, after their penetration into organisms, will undergo, thanks to the
detoxifying enzymes, metabolic transformations.
B. These detoxifying enzymes increase the water solubility of the molecules they support in order
to facilitate their elimination from the body.
C. Biotransformation reactions are divided into three reactions: phase I, phase II and phase III.
D. Phase I is provided by enzymes which catalyze the oxidation and functionalization of a
xenobiotic by a monooxygenation reaction so as to make it more reactive, which facilitates
subsequent metabolism.
E. This phase essentially involves cytochrome P450 monooxygenases (CYP).
F. Phase II is carried out by enzymes which catalyze the conjugation of functionalized molecules
to endogenous substrates making the xenobiotic more soluble by forming a hydroxyl compound
having a water-soluble property by adding endogenous hydrophilic compounds (glutathione,
acetate, sulfate, etc.).
G. These enzymes are involved both on xenobiotics entering the cell and on molecules previously
modified by phase I enzymes. Among these enzymes the most solicited is glutathione S-
transferases (GST).
H. Phase III enzymes are excretion enzymes grouping together membrane proteins capable of expelling
out of the cell a xenobiotic modified by the phase I and / or phase II enzymes.
  Biomarkers of effect:
The effect biomarkers correspond to a biological alteration which, depending on the intensity of the
response, may be associated with an alteration in the physiological and cellular state of the individual.
And depending on its magnitude, can be recognized as a health disorder or disease (Halliwell &
Gulferidge, 1999).
These biomarkers are said to be non-specific and they generally reflect damage at the physiological level
such as growth and reproduction or at the cellular level such as metabolic nerves, energy production and
cellular respiration.
 Sensitivity biomarkers:
According to Who (1993), sensitivity biomarkers indicate that the organism has already been subjected to
the same pollutants and that it has adapted to them. We can cite resistance; it is mainly genetic
modifications.
Other authors define sensitivity biomarkers as the existence of a different sensitivity to the toxicant in a
part of the population. And characterize the individual and population variations specific to the response
to exposure to a toxicant.
3). Characteristics of biomarkers:
▫ The biomarker response must be sensitive, specific and early.
▫ Their sensitivity and specificity with respect to a type of pollution or stress must be known.
▫ Their measurement must be reproducible over time, in the short and / or long term.
▫ They must be common to individuals of the same population, and the variability within a control or
exposed group must be known.
▫ The methods of their determination must take into account various factors of applicability in the
laboratory and in the field such as ease of sampling and storage and the cost of analyzes.
▫ They must have a predictive power of effects at higher biological levels (growth, reproduction,
population, etc.) and possibly predict risks for humans.
▫ The biomarkers are distributed according to a graduation of decreasing specificity from those with
the highest specificity to those non-specific which reflect penal plysiotoxicological reactions.
4). The purpose of Biomarkers:
 The diagnosis: allows to identify the presence of a disease (abnormal state of health of the
organism);
 The prognosis: allows to determine the foreseeable evolution of the state of health of the organism;
 The mechanism: accounts for the effect observed downstream of the treatment;
 Illness (state of health): reflects the consequence or measure of the state of health (quality);
 Efficacy (efficacy BM): reflects the beneficial outcome of the treatment;
 Toxicity (toxicity BM): accounts for the toxicological effect of the product on the organism;
 The stage: makes it possible to distinguish between different stages of health (Eurasanté, 2005).