Radiation Effects on Macromolecules

Radiation Effects on Macromolecules

• Radiation effects on macromolecules can manifest through main-chain scission, cross-linking, and point lesions

Main-Chain Scission

• Main-chain scission involves the breaking of long-chain structures of macromolecules like DNA, proteins, and polysaccharides
• This results in reduced function of macromolecules, leading to cellular malfunction
• If DNA is affected and not repaired properly, mutations may develop, potentially leading to cancer
• This effect is used in radiation therapy to break down cancer cell DNA and prevent replication

Cross-Linking

• Cross-linking involves abnormal bonds between macromolecules or within a single molecule, preventing normal function
• This can inhibit cellular processes, leading to apoptosis
• Faulty DNA repair can cause mutations and increase the risk of secondary cancers
• Some cancer cells survive radiation therapy by forming excessive cross-links, making them resistant to treatment

Point Lesions

• Point lesions are small-scale chemical changes in macromolecules, including base alterations in DNA
• This leads to mutations, potentially resulting in carcinogenesis if proliferated
• Radiation-induced point mutations are a risk for secondary cancers after radiotherapy

Radiation Effects on Chromosomes

• Radiation can have several effects on chromosomes, including terminal deletion, dicentric formation, and ring formation

Terminal Deletion

• Terminal deletion involves the loss of a chromosome end due to radiation-induced breakage
• This leads to genetic instability, possibly resulting in cancer or cell death
• Terminal deletion is observed in patients receiving radiation therapy where high doses damage hematopoietic cells, increasing leukemia risk

Dicentric Formation

• Dicentric formation is the abnormal fusion of two chromosome fragments with two centromeres
• This causes mitotic failure and cell death, which is useful in targeting cancer cells
• Dicentric chromosomes can indicate lethal damage to cancer cells after radiation therapy

Ring Formation

• Ring formation occurs when chromosomal ends fuse into a circular structure due to radiation-induced damage
• This prevents normal chromosome segregation, leading to nonviable cells
• This is seen in cells exposed to radiotherapy for aggressive tumors

Radiation Effects on DNA

• Radiation can cause single-strand breaks, double-strand breaks, cross-linking, and rung breakage in DNA

Single-Strand Breaks

• A single-strand break is when only one strand of DNA is broken
• If the repair fails, this results in mutations
• This is repaired efficiently in normal cells but can accumulate in cancer therapy-resistant tumors

Double-Strand Breaks

• Double-strand breaks occur when both strands of DNA are broken
• If these breaks are misrepaired, it can lead to chromosomal translocations and cancer
• This is a major mechanism of tumor control in radiation therapy

Cross-Linking of DNA

• Cross-linking of DNA involves DNA strands abnormally bonding together
• This prevents replication and transcription, causing apoptosis
• It is used in radiation therapy to disable tumor DNA repair

Rung Breakage

• Rung breakage damages the nitrogenous bases of DNA
• This can lead to carcinogenesis
• Rung breakage is linked to secondary cancer risks post-radiotherapy

Sequence of Radiation Injury

• The sequence of radiation injury includes the latent period, the period of injury, and the recovery period

The Latent Period

• The latent period is the time between exposure to x-rays and the appearance of radiation damage
• This is the first step in the sequence of radiation injury
• The latent period can be short or long, based on the total dose of radiation received and the amount of time or rate it took to receive the dose
• The more radiation received and the faster the dose rate, the shorter the latent period

The Period of Injury

• A variety of cell injuries may occur during this phase: cell death, changes in cell function, breaking or clumping of chromosomes, formation of giant cells, abnormal cell division or cessation of cell division

The Recovery Period

• Not all cellular radiation injuries are permanent
• Most low-level radiation injury is repaired within the body's cells
• Scatter radiation remains in cells, but the body can remove it in 24-48 hours
• Repeated exposure inhibits the body's ability to adjust

Cumulative Effect

• The effects of radiation exposure are additive, and unrepaired damage accumulates in the tissues
• The cumulative effects of repeated exposure can lead to cancer, cataract formation, and birth defects

Somatic Effects

• Somatic effects occur in all cells of the body except the reproductive cells
• The changes in somatic effects are not passed along to future generations
• Somatic effects only affect the individual exposed, and the primary consequence is cancer

Genetic Effects

• Genetic effects occur in reproductive cells
• They are passed along to future generations
• Genetic effects do not affect the exposed individual but are passed along by mutations in offspring
• Genetic damage cannot be repaired

Short-Term Effects

• Short-term effects include death, skin burns (erythema), hair loss (epilation), sterility, and cataracts
• High doses of radiation over short periods of time tend to kill cells

Long-Term Effects

• Long-term effects include chronic or long-term effects that may not be observed for many years
• These are associated with low doses of radiation over an extended period of time

Stochastic (Probabilistic) Effects

• Stochastic effects result from low doses delivered over a long period
• Stochastic effects include radiation-induced malignancy and genetic effects
• Radiation exposures in diagnostic radiology are low and have low LET, they are chronic in nature because they are delivered intermittently over long periods
• Therefore, stochastic radiation effects are of particular importance

Local Tissue Effects

• Skin damage caused by early fluoroscopic examinations without protective gear is radiodermatitis

Cataracts

• In 1949, the first paper reporting cataracts in cyclotron physicists appeared and By 1960, several hundred cases of radiation-induced cataracts had been reported

Radiation-Induced Cataracts

• Radiosensitivity of the lens of the eye is age-dependent
• As the age of the individual increases, the radiation effect becomes greater, and the latent period becomes shorter
• Radiation-induced cataracts occur on the posterior pole of the lens
• Latent periods ranging from 5 to 30 years have been observed in humans, and the average latent period is approximately 15 years

Radiation Hormesis

• Radiation hormesis suggests that low levels of radiation—less than approximately 100 mGy (10 rad)—are potentially beneficial
• Such low doses may provide a protective effect by stimulating molecular repair and immunologic response mechanisms
• Radiation hormesis remains a theory, and ALARA will continue to be practiced

Somatic Deterministic Effects

• Somatic deterministic radiation-induced damage occurs in the exposed individual
• Severity increases as the radiation dose increases
• The deterministic effects have a clear threshold dose, meaning they only occur if the dose exceeds a certain level

LD 50/60

• The LD 50/60 is the dose of radiation to the whole body that causes 50% of irradiated subjects to die within 60 days
• 1 Gy dose means no expected death
• A dose >6 Gy means no survivor unless with medical support
• A dose >10 Gy means no survivors

Mean Survival Time

• As the whole-body radiation dose increases, the average time between exposure and death decreases
• A higher dose is associated with faster death

Local Tissue Damage

• Exposure is localized to specific parts of the body
• A higher dose is required to produce a response, unlike whole body exposure

Skin Erythema (Reddening of the Skin)

• Damage to basal cells of the skin occurs at doses above 2 Gy, with symptoms appearing hours to weeks after exposure

Cataracts Formation

• Lens opacities can develop at doses exceeding 0.5 Gy and may lead to vision impairment over time

Sterility (Temporary or Permanent)

• Temporary sterility occurs around 2 Gy
• Permanent sterility occurs above 5 Gy

Epilation (Hair Loss)

• Epilation occurs only when the radiation dose exceeds a specific threshold
• Temporary hair loss occurs with ≥3 Gy
• Permanent hair loss after 27 Gy

Genetic Effects

• Radiation-induced genetic mutations in germ cells (sperm and egg) can lead to inherited diseases, birth defects, or other genetic disorders

Microcephaly

• Microcephaly refers to abnormal brain development resulting in a smaller-than-normal head size in newborns

Growth Retardation

• Growth retardation is delayed physical growth in offspring due to DNA damage in reproductive cells

Factors Affecting Radiation Response

• Dose and Dose Rate: Higher doses and dose rates cause more severe effects
• Type of Radiation: High-LET radiation (alpha particles, neutrons) causes more biological damage than low-LET radiation (X-rays, gamma rays)
• Tissue Sensitivity: Rapidly dividing cells (e.g., bone marrow, intestinal lining) are more sensitive to radiation
• Oxygenation (Oxygen Effect): Oxygen enhances radiation damage, making oxygen-rich tissues more vulnerable
• Age and Developmental Stage: Younger individuals and embryos are more sensitive to radiation effects