X-rays as a physical immunosuppressant
Based on the direction of its biological effect, X-radiation (along with γ-radiation) is classified as an immunosuppressive agent (immunosuppressant). As a physical impact factor, it is capable of totally suppressing the functioning of the immune system and the activity of immunocompetent cells.
In the general classification of agents affecting immune processes, irradiation occupies a distinct niche among other suppressors, which also include:
- Cytostatics (purine antagonists, e.g., 6-mercaptopurine, and amino acid antagonists).
- Hormonal agents (various glucocorticosteroids).
- Biological agents (monoclonal antibodies to cell receptors, antilymphocyte serum).
- Calcineurin inhibitors (tacrolimus, sirolimus).
Due to the pronounced suppression of the body's defenses, any radiation exposure requires strict dosing and monitoring.
Mutagenic effect: focus on deletions
In addition to immunosuppression, X-radiation represents a classic physical mutagen. Its effect on DNA leads to point (gene) mutations, which typically alter a single nucleotide pair.
The most characteristic genetic consequence of X-ray irradiation is deletions — the loss of one or more nucleotides from the DNA chain. The consequences of such a mutation directly depend on the amount of lost material:
- Loss of a number of nucleotides that is a multiple of 3 (without a frameshift). The synthesized protein is shortened by one or more amino acids. The primary sequence of the polypeptide chain after the mutation point is otherwise preserved.
- Loss of a number of nucleotides that is not a multiple of 3 (with a frameshift). This is the most destructive scenario, completely disrupting the future protein structure.
Frameshift mechanism
The reading frame (frameshift) is the nucleotide sequence from the initiation codon to the termination codon, strictly divided into triplets that encode amino acids.
If X-radiation causes a deletion of a number of nucleotides not divisible by three, the boundaries of all subsequent triplets are shifted. As a result, all genetic information after the mutation point is read incorrectly. Instead of the required protein, a peptide with an entirely random amino acid sequence is synthesized.
A frequent consequence of such a shift is the premature appearance of a stop codon shortly after the mutation. Premature translation termination occurs, resulting in a shortened and functionally inactive molecule.
Example of radiation-induced protein damage
To illustrate how a deletion destroys a protein, let us consider a typical situational problem.
Normally, a messenger RNA segment codes for the amino acids Leucine—Lysine. If an X-ray-induced deletion of just a single nucleotide (e.g., adenine) occurs, the reading frame shifts. Completely new triplets are formed (e.g., CCA—AGU), which now code for the amino acids Proline—Serine instead of the original ones. A complete substitution of the amino acid sequence takes place, and the synthesized protein completely loses its functional activity.
Impact at the chromosomal level
The pathological impact of X-radiation is not limited to point defects of individual genes. At a higher, chromosomal level, this physical factor causes extensive rearrangements of genetic material, which are formally classified as chromosomal aberrations.
Such major radiation-induced damages include:
- Deletions of large chromosomal segments.
- Duplications (pathological doubling of fragments).
- Translocations (transfer of a segment to another chromosome).
- Inversions (rotation of a large chromosomal segment).
The combination of these damages explains the high danger of uncontrolled irradiation for living cells.
The phrase «X-rays wreck the frame» helps remember the main type of gene mutation caused by irradiation — radiation causes the loss (deletion) of nucleotides, leading to a frameshift.
Class and exam questions
To which group of immunotropic factors does X-radiation belong?
In the classification of agents affecting immune processes, it belongs to physical immunosuppressants, meaning it suppresses immunity.
What type of point mutation is most characteristic of X-ray exposure?
X-radiation most commonly provokes deletions — the loss of one or more nucleotides from the DNA chain.
What happens when a number of nucleotides not divisible by three is lost?
A frameshift occurs. The meaning of all subsequent codons is completely altered, resulting in the synthesis of a protein with a random amino acid sequence, or the process is aborted due to a stop codon.
Does X-radiation cause chromosomal aberrations?
Yes, at the chromosomal level it causes extensive rearrangements: large deletions, duplications, translocations, and inversions of chromosome segments.
What else to study on this topic
- Mechanisms of other point mutations: substitutions (missense and nonsense mutations), transitions, and transversions.
- Chemical mutagens: how acridine compounds distort the structure of the DNA double helix.
- Biological factors of mutations: the role of transposons (mobile genetic elements) in nucleotide insertions.
- Pharmacological immunosuppressants: mechanism of action of cytostatics and monoclonal antibodies (infliximab).
- Dynamic mutations: trinucleotide repeat expansion and blockade of gene transcription.
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