Late Effects of Radiation and Epidemiology

Late Effects of Radiation

• Radiation-induced damage at the cellular level can lead to somatic and hereditary damage later in life.
• Late effects are the long-term results of radiation exposure.
• Measurable late biologic damage includes cataracts, leukemia, and genetic mutations.

Epidemiology

• It deals with the incidence, distribution, and control of disease in a population.
• Studies consist of observations and statistical analysis of data such as the incidence of disease within groups.
• It include the risk of radiation-induced cancer.
• This is valuable to radiobiologists for formulating dose-response estimates to predict cancer risk in exposed populations
• Carcinogenesis (Tumorigenesis) is the formation of cancer.

Radiation Dose-Response Relationship

• Demonstrated graphically by a curve that maps observed effects of radiation exposure vs. dose.
• Information can be used to predict the risk of malignancies in human populations exposed to low levels of ionizing radiation.
• The curve is either linear or nonlinear, depicting either a threshold or nonthreshold dose.
• Curve 1 (linear/nonthreshold) represents any stochastic effect like cancer and Curve 2 & 3 (linear / threshold, nonlinear / threshold) represents side effects such as leukopenia and skin erythema.

Threshold and Nonthreshold Relationships

• Threshold: the point at which a response/reaction to stimulation first occurs.
• For ionizing radiation, a threshold means no biologic effects are observed below a certain radiation level/dose.
• Biologic effects begin only when the threshold level/dose is reached.
• Nonthreshold: any radiation absorbed dose has the capability of producing a biologic effect.

Linear Nonthreshold (LNT) Curve

• It is caused by ionizing radiation in living organisms in a directly proportional manner all the way down to dose levels approaching zero.
• No radiation dose can be considered absolutely safe.
• The probability of biologic effects increases directly with the magnitude of the absorbed dose.
• (Dose = Probability of Effect), the increase in dose does not increase the severity
• Used for ALARA (As Low As Reasonably Achievable) and late stochastic effects such as Carcinogenesis.
• The model exaggerates the seriousness of radiation effects at lower doses from low-LET radiation.

Linear Threshold (LT) Curve

• "Linear" means the severity of the biologic effect is directly proportional to the dose.
• "Threshold" means a biologic response does not occur below a specific dose level.
• (Dose = Severity of Effect↑)
• Used for acute reactions from significant radiation exposure such as Acute Radiation Syndrome (ARS) symptoms.

Nonlinear Threshold (NLT) Curve

• Also known as a sigmoid (S-shape).
• Nonlinear: The severity of the biologic effect is directly related to the dose (Not directly proportional).
• Threshold: A biologic response does not occur below a certain dose level.
• Used for radiation therapy to demonstrate high-dose cellular response to the radiation absorbed; also, tissue reactions (skin erythema, cataract).

Somatic Effects

• Effects of ionizing radiation sustained by the body of the irradiated person.
• Classified as Tissue Reactions (Deterministic effects): Early (skin erythema) and Late (Cataracts, stericlty).
• Classified as Stochastic effects (Nondeterministic effects): Carcinogenesis

Late Somatic Effects

• Consequences of radiation exposure appear months or years after exposure.
• Effects may result from previous acute, high radiation doses or long-term low-level doses sustained over several years.
• Low-level doses are a consideration for patients and personnel exposed to ionizing radiation.
• The risk estimate for humans contracting cancer from low-level radiation exposure is still controversial.
• 3 major types of late effects are cataractogenesis, carcinogenesis, and embryologic effects.

Carcinogenesis

• Cancer is the most important late stochastic effect caused by exposure to ionizing radiation.
• A random occurrence that does not have a threshold (nonthreshold), and the severity of the disease is not dose-related.
• It may take 5 or more years to develop in humans.
• Cancer caused by low-level radiation is difficult to identify.

Human Evidence for Radiation Carcinogenesis

• Radium watch-dial painters (1920s and 1930s)
• Uranium miners (early years, and Navajo people of Arizona and New Mexico during the 1950s and 1960s)
• Early medical radiation workers (radiologists, dentists, technologists) (1896 to 1910)
• Japanese atomic bomb survivors (1945)
• Patients with benign postpartum mastitis who were given radiation therapy treatments (mid 1900s)
• Evacuees from the Chernobyl nuclear power station disaster in 1986

Life Span Shortening

• Laboratory experiments on small animals have shown that the life span of small animals that were exposed to nonlethal doses of ionizing radiation was shortened as a consequence of the exposure.
• Studies of the life span of US radiologists indicated that radiologists had a shorter life span than non-radiologist physicians (the conclusions were questionable).
• Shortening of the life span in both animals and humans was the result of cancer and leukemia.

Cataractogenesis

• Late somatic tissue reaction
• There is a high probability that a single dose of approximately 2 Gy will induce the formation of cataracts, resulting in lost vision.
• Radiation-induced cataracts in humans follow a threshold, nonlinear dose-response relationship.
• Recent data: a threshold for single exposures is now considered to be 0.5 Gy.
• Lengthy fluoroscopic procedures can result in radiation exposure to the lens of the eye from cumulative scatter radiation.

Embryologic Effects (Birth Defects)

• There are 9 months in the human pregnancy period
• Stages of gestation in humans: preimplantation (0 to 9 days after conception), organogenesis (10 days postconception to 12 weeks), and fetal stage (12th week to term).
• The first trimester is the most crucial period concerning harmful consequences from irradiation.
• Developing central nervous and sensory organs of the embryo-fetus contain many stem cells during this period.
• High radiation doses to the embryo within approx. 2 weeks of fertilization (before organogenesis) can result in fetal death, followed by spontaneous abortion.
• Developing fetus is most susceptible to radiation-induced congenital abnormalities during organogenesis (10 days and up to 12 weeks after conception).
• Abnormalities may include: growth inhibition, intellectual disability, microcephaly, genital deformities, sensory organ damage.
• Fetal radiosensitivity decreases as gestation progresses.

Genetic (Hereditary) Effects

• Biologic effects of ionizing radiation on future generations.
• Caused by radiation-induced damage to the DNA molecule in sperm or ova, and result in genetic disorders or diseases.
• Spontaneous mutations can be transmitted from one generation to the next and cause a variety of disorders or diseases, including hemophilia, Huntington's chorea, sickle cell anemia, cystic fibrosis, hydrocephalus, Down syndrome, and Duchenne's muscular dystrophy.

Doubling Dose Concept

• "Doubling dose" means doubling chances of offspring born w/ mutation
• The radiation dose causes the number of spontaneous mutations occurring in a given generation to double their original occurrence.
• Doubling Dose Concept:
  • Percentage (%) of offspring born in each generation with spontaneous mutations %: 7%.
  • Estimated radiation dose in sieverts (Sv) received: 1.56 Sv
  • Percentage (%) of offspring born with the equivalent mutation, after a doubling equivalent dose %: 14%.