Cytogenetic biomonitoring

De nombreuses études ont étudié le lien potentiel entre les champs électromagnétiques d’extrêmement basses fréquences (CEM-EBF) et la santé au cours des 40 dernières années. L’exposition « court terme/intensité élevée » est bien étudiée chez les volontaires humains et les animaux. Les effets observés ont des seuils en deçà desquels ils ne se produisent pas et peuvent être évités en respectant les restrictions de base appropriées (champs électriques induits dans le corps).

Des questions se posent quant à l’exposition « long terme/faible intensité ». Les CM-EBF sont classés par le CIRC comme “potentiellement cancérigènes pour l’homme” sur base de données épidémiologiques montrant un risque accru de leucémie infantile.  D’autres études soulèvent la question du rôle des CEM 50 Hz dans le développement du cancer, de la maladie d’Alzheimer et d’autres maladies. Cependant, les études ne permettent pas de conclure et des recherches approfondies sont nécessaires.

Il est donc important de déterminer les conséquences biologiques dans des groupes particulièrement exposés, comme par exemples les travailleurs exposés aux CEM. Une étude de biomonitoring cytogénétique est utile pour déterminer si les CEM-EBF peuvent induire des dommages génétiques.

Qu’est-ce qu’une étude de biomonitoring cytogénétique et comment pourrait-elle aider à comprendre les effets des CEM sur la santé ? Voici comment une telle étude est menée et comment elle doit être interprétée.

Human Biomonitoring has been defined as “monitoring activities in human beings, using biomarkers that focus on environmental exposures, diseases and/or disorders and genetic susceptibility, and their potential relationships” (http://www.eu-humanbiomonitoring.org/).

A biomarker, or biological marker, is something that can be measured in the human body. For example, it is of interest to evaluate exposure to toxic agents in the environment, by measuring their presence in blood or urine for example. There are several different categories of biomarkers (Verschaeve, 2015):

• Biomarkers of exposure: They are early effect markers. They show the presence of something that may result, but did not evolve yet, in disease or damage, e.g. increased mercury levels in the blood reflecting excessive exposure to this metal or benzene metabolites in urine for traffic-related pollution.
• Biomarkers of effects: They show a biological effect that can be associated with an established or possible illness or with precursors of illness, e.g. the concentration of beta-microglobulin in urine or cystatin C in serum as markers for renal insufficiency.
• Biomarkers of susceptibility/sensitivity: They are indicators of innate or acquired susceptibilities against certain agents and in the development of particular diseases, e.g. variations of certain genes that are associated with breast cancer.

A cytogenetic biomonitoring study aimed to detect changes in the genetic materials (chromosomes) of cells.

This is of importance because a link has been established between observed genetic damages in cells of people and an increased cancer risk. Figure 1 shows the sequence of events linking exposure to a genotoxic agent and the development of a disease:

Figure 1 – Sequence of events linking exposure to a genotoxic agent and the development of a disease

The increased frequency of structural chromosome aberrations is considered as a biomarker of both exposure and effect.

De nombreux tests sont disponibles pour vérifier les effets d’un agent sur les cellules. Voici quelques-uns des plus importants : le test du micronoyau/cytome et le test de comète.

Les lymphocytes humains sont des cellules utiles et facilement accessibles pour évaluer l’ampleur et/ou l’effet cumulatif de l’exposition à des agents génotoxiques.  D’autres cellules, par exemple les cellules buccales exfoliées, sont parfois aussi utilisées.

Contrarily to biomonitoring considering only specific markers (e.g., heavy metals), cytogenetic biomonitoring studies integrate exposures to all (genotoxic) agents. They can be conducted on people allegedly exposed to any agent of risk, including electromagnetic fields, to determine whether or not agents in the environment or in the workplace induce genetic damage in the investigated human cells.

Increased frequencies of genetic damage in cells from exposed vs. unexposed control subjects mean that there was an abnormal high exposure to (an) agent(s) able to damage the hereditary material and hence potentially able to induce cancer and other related diseases. A shortcoming of a cytogenetic biomonitoring study is that an increased frequency of genetic damages cannot be directly linked to (a) defined agent(s). It is particularly interesting as a ‘first line’ study, to quickly and globally test the environment around homes or workplaces.

Let’s see how such studies need to be conducted to provide useful results.

In (cytogenetic) biomonitoring studies two different populations are compared (e.g. radiation exposed subjects versus non-irradiated controls, etc.). The selection of the test persons is very crucial. It should be carefully done in order to avoid confounders as much as possible (figure 2). Confounders are other agents or characteristics/habits of people that could also enhance the frequencies of chromosomal damages. They can therefore influence the test results. Typically, to avoid confounders, both populations need to be as identical as possible with respect to their age distribution, gender, smoking habits, drug use or drinking behaviour, their social status, their origin and medical history (e.g., recent diagnostic irradiations, medications, viral infections).

Sample collection from volunteers should thus best be accompanied by carefully designed interviews or by questionnaires that consider these factors.

The studied populations should furthermore be large enough and the number of (blood)cells investigated should also be large enough to obtain sufficient statistical power.

Figure 2 – Confounders in cytogenetic biomonitoring

Interpreting such trials is tricky and requires comparison with a matched control group, as described above. Moreover results are mainly interpretable at the group level and not at the individual level, as no limit decision values for cancers or other diseases are defined. However some further analysis should be conducted to apprehend the origin of unexpectedly high level of genetic damages in a particular individual.

In interpreting the results, a decision-making tree is applied (figure 3)

Figure 3 – Decision-making tree in cytogenetic biomonitoring

In case effects are observed at group level some measures should be envisaged to lower the exposure level. In occupational exposure, the aim will be to create better working conditions through implementation of measures to reduce exposure to mutagens/carcinogens in the work environment.

As results are mainly interpreting at group level, cytogenetic biomonitoring studies cannot be used to select workers and exclude the more susceptible ones.

The primary purpose of cytogenetic biomonitoring is scientific bearing in mind the protection of people’s health. It must be seen as a tool for the biosurveillance of carcinogenic risks related to the environment and the workplace.

• Information sur les types de recherches en PDF (882 Ko)
• Verschaeve, L. (2015). Genetic toxicology: tests and applications. Antwerpen, Belgium: University Press Antwerp.

• Une seule étude, ce n’est pas assez!