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Individual radiation sensitivity
- The term "radiation sensitivity" describes the sensitivity of organisms to the effect of ionising radiation.
- The cause of radiation sensitivity may be the insufficient repair and/or misrepair of the radiation-damaged genetic material of the cells (DNA), for instance due to defective repair mechanisms.
- The individual genetic makeup of each single person determines his or her radiation sensitivity or radiation resistance.
- Over the next few years biomarkers and bioassays for estimating individual radiation sensitivity in the moderate to high dose range could become available allowing routine and reliable identification of individuals with increased radiation sensitivity.
The term "radiation sensitivity" describes the sensitivity of organisms to the effect of ionising radiation. This can relate to the level of individual cells, tissues and organs and may thus affect the whole organism. Certain alterations to the genetic material can lead to a dramatic change in radiation sensitivity. Already early in the history of radiotherapy, it became evident that individuals respond differently to radiation. This was reflected, among other things, in the increased occurrence of acute side effects and/or of late effects such as secondary malignant diseases.
DNA repair defects as possible cause of overreactions
The cause of such overreactions may be the insufficient repair and/or misrepair of the radiation-damaged genetic material of the cells (DNA), for instance due to defective repair mechanisms. An example of such repair defects is a mutated AT gene which is referred to as ATM in its altered form and leads to the clinical syndrome called "Ataxia telangiectasia" ("Louis-Bar Syndrome").
These patients display severe side effects already during or after radiotherapy, in many cases leading to the sudden death of the patient shortly after early termination of the therapy. Other side effects of radiotherapy on normal tissue such as skin reddening and tissue death are also linked to individual radiation sensitivity.
Association between radiation sensitivity and disease (genetic predisposition)
Experimental studies on cells and tissues of patients bearing a wide variety of diseases such as cancer, diseases of the nervous system, immune system or of premature ageing are associated with increased radiation sensitivity. As these clinical phenotypes belong to diverse groups of diseases, there is no uniform clinical presentation of "radiation sensitivity".
The individual genetic makeup of each single person determines his or her radiation sensitivity or radiation resistance. However, which determining factors are responsible in particular, remains largely unknown apart from a few specific individual diseases.
The degree of radiation sensitivity depends on the combination of various genetic traits and how they interact with each other. Also hormonal balance, the immune system and various environmental factors (infections, harmful substances, pollutants and diet) may influence the outcome of radiation sensitivity.
Alterations of gene products determine radiation sensitivity
Variation in radiation sensitivity may be partly caused by changes in gene products (proteins), which ensure that the genetic material (DNA) is maintained and damage is repaired. Cellular and clinical studies associate some of these changes with increased radiation sensitivity. Altered cell growth or - in the case of irreparable cell damage – self-induced controlled cell death (apoptosis) are individual parameters for radiation sensitivity as well.
It is assumed that the proportion of radiosensitive individuals ranges from five to ten per cent of the general population. With tumour patients, however, this proportion can be higher and may amount to 30 - 40 per cent.
Methods for predetermining radiation sensitivity
In some cases, individuals with certain gene alterations display a clinical phenotype, for example patients with "Ataxia telangiectasia" (Louis-Bar Syndrome), so the clinical method of treatment can be adapted accordingly. However, in most cases radiosensitive individuals are inconspicuous in appearance.
Biomarkers or Bioassays to detect radiation sensitivity
At the moment, in vitro assays based on molecular biological, cytogenetic and cellular methods are being developed for the identification of highly radiosensitive individuals. When considering radiation sensitivity within the cell system, traits such as cell survival are measured. For this purpose, cells are exposed to radiation in the laboratory and are then further cultured in order to be able to determine the number of surviving cells. Also the ratio between self-induced and uncontrolled cell death can be an indicator for radiation sensitivity.
Test systems at the DNA level
Test systems at the DNA level are, for example, the analysis of chromosomal damage in which case misrepaired DNA breaks are detected after radiation exposure. The DNA repair capacity of cells can also be investigated directly by detection of residual DNA strand breaks. Commonly used methods for this purpose are
- the Comet assay (technique for determining the number of radiation-induced DNA breaks in the cell nucleus),
- the gamma-H2AX assay (technique for visualising repair proteins at radiation-induced DNA double strand break sites), as well as
- the recording of the mutation frequency, for example, by determining a defined base sequence on the DNA.
Significance for radiation protection
Methods for determining individual radiation sensitivity would be particularly desirable before starting radiotherapy or in connection with a radiation accident.
In the case of radiotherapy, the treatment plan could be adapted individually according to the radiation sensitivity of the patient. In this way it might be possible to significantly reduce side effects.
Treatment of radiation accident victims
In the event of a radiation accident and high dose exposure, the victim's probability of survival depends directly on the individual reaction to the dose received. If information on individual radiation sensitivity were quickly available by means of biological indicators capturing the influence of individual radiation sensitivity (blood count, chromosomal aberrations, micronuclei), it could guide the attending physicians in choosing the appropriate therapy.
Knowing about a patient's individual radiation sensitivity would be very helpful, especially in the case of exposure to moderate and high doses (therapy, accident). In the low dose range (below limit values) and within the variation range of natural radiation exposure, the benefit of being informed about radiation sensitivity is doubtful. Over the next few years biomarkers and bioassays for estimating individual radiation sensitivity in the moderate to high dose range could become available allowing routine and reliable identification of individuals with increased radiation sensitivity.
Whether the detection methods for radiation sensitivity in the high dose exposure range can also provide specific and reliable information about the risk for low doses, can currently not be predicted. This question has to be resolved before using such diagnostic techniques for low dose ranges which could among other things be relevant for occupational safety and rescue services. However, attention should then also be given to data protection, ethical aspects and personal rights.
State of 2018.11.30