Stochastic Effects & Late Tissue Reactions

• Chapter 9 focuses on stochastic effects and late tissue reactions of radiation in organ systems

Late Effects of Radiation

• Radiation-induced cellular damage can lead to measurable somatic and hereditary damage later in life
• Late effects are the long-term results of radiation exposure with measurable biologic damage including:
  • Cataracts
  • Leukemia
  • Genetic mutations

Epidemiology

• Epidemiology is the study of the incidence, distribution, and control of disease in a population
• Epidemiologic studies include observations, statistical analysis of data, and the risk of radiation-induced cancer within groups
• Radiobiologists use this information to make dose-response estimates to predict cancer risk in human populations exposed to ionizing radiation
• Carcinogenesis (tumorigenesis), the formation of cancer, is a primary stochastic effect

Radiation Dose-Response Relationship

• Radiation dose-response relationship is graphically demonstrated through a curve
• The curve maps the observed effects of radiation exposure in relation to the received radiation dose
• Information from these curves are used to predict the occurrence of malignancies in human populations exposed to low levels of ionizing radiation
• The curve can be linear or nonlinear, and depicts either a threshold or nonthreshold dose

Threshold and Nonthreshold Relationships

• Threshold: a point at which a response or reaction to increasing stimulation initially happens
• With ionizing radiation, threshold means no biologic effects are observed below a certain radiation level or dose
• Biologic effects begin to occur only when the threshold level or dose is reached
• Nonthreshold: indicates that a radiation absorbed dose of any magnitude produces a biologic effect

Linear Nonthreshold (LNT) Curve

• LNT curve means radiation in living organisms causes effects in a directly proportional manner, down to zero dose levels
• No radiation dose is considered absolutely safe
• The probability of biologic effects increases directly with the magnitude of the absorbed dose
• ALARA and late stochastic effects, such as carcinogenesis, utilize LNT curves
• The linear dose-response model has the potential to exaggerate the seriousness of radiation effects at lower dose levels from low-LET radiation

Linear Threshold (LT) Curve

• LT curve means the severity of the biologic effect is directly proportional to the dose
• Threshold is the point where the biologic response does not occur below a specific dose level
• LT is used for acute reactions from significant radiation exposure, such as ARS symptoms like skin erythema and hematologic depression

Nonlinear Threshold (NLT) Curve

• AKA sigmoid (S-shape) curve
• NLT curve means the severity of the biologic effect is directly related to the dose, but not directly proportional
• Threshold is the point where the biologic response does not occur below a specific dose level
• Radiation therapy demonstrates high-dose cellular response to radiation absorbed within locations like skin, the lens of the eye, and various types of blood cells utilizes NLT curves
• Tissue reactions, such as skin erythema and cataracts, utilize NLT curves

Somatic Effects

• The effects of ionizing radiation include tissue reactions (deterministic effects) and stochastic effects (nondeterministic effects) for the irradiated person
  • Early tissue reactions: skin erythema
  • Late tissue reactions: cataract
  • Stochastic effects: Carcinogenesis

Late Somatic Effects

• Consequences of radiation exposure appear months or years after said exposure
• Results from previous whole- or partial-body acute exposure, previous 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
• Human risk estimates for humans contracting cancer from low-level radiation exposure remains controversial
• Three major types of late effects:
  • Cataractogenesis
  • Carcinogenesis
  • Embryologic effects

Carcinogenesis

• Cancer is a significant late stochastic effect caused by exposure to ionizing radiation
• It is a random occurrence without a threshold (nonthreshold)
• Disease severity is not dose-related
• Can take 5+ years to develop in humans
• Cancer caused by low-level radiation is difficult to identify

Human Evidence for Radiation Carcinogenesis

• Important examples include:
  • Radium watch-dial painters (1920s-1930s)
  • Uranium miners and Navajo in Arizona/New Mexico (1950s-1960s)
  • Early medical radiation workers (1896-1910)
  • Japanese atomic bomb survivors (1945)
  • Patients with benign postpartum mastitis (mid 1900s)
  • Evacuees from the Chernobyl disaster (1986)

Life Span Shortening

• Lab experiments on small animals prove nonlethal doses of ionizing radiation shortens their life span as a consequence of exposure
• Studies indicate that U.S. radiologists have shorter life spans than non-radiologist physicians
• Epidemiologic studies reveal that early death in both animals and humans results from cancer and leukemia

Cataractogenesis

• There is a high probability that a single dose of ~2 Gy will induce the formation of cataracts
• Cataractogenesis results in partial or complete vision loss
• Radiation-induced cataracts in humans follow a threshold, nonlinear dose-response relationship
• The threshold for single exposures is now considered to be 0.5 Gy
• Very lengthy fluoroscopic procedures can cause significant radiation exposure to the lens of the eye from cumulative scatter radiation

Embryologic Effects (Birth Defects)

• Stages of gestation in humans:
  • Preimplantation (0-9 days after conception)
  • Organogenesis (10 days postconception to 12 weeks)
  • Fetal stage (12th week to term)
• The first trimester is the most crucial period concerning harmful consequences from irradiation
• Developing central nervous system and sensory organs of the embryo-fetus contain a high number of stem cells during this period
• If the embryo receives a high dose of radiation within ~2 weeks of fertilization (before organogenesis = fetal death)
• Apparent negative consequence = spontaneous abortion

Embryologic Effects (Birth Defects) Continued

• A developing fetus is most susceptible to radiation-induced congenital abnormalities in the 10-12 weeks after conception
• Abnormalities 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 impact future generations
• Genetic mutations caused by radiation-induced damage to DNA in sperm or ova
• Spontaneous mutations can be transmitted and cause a wide variety of disorders including:
  • Hemophilia
  • Huntington's Chorea
  • Down syndrome
  • Duchenne's muscular dystrophy
  • Sickle cell anemia
  • Cystic Fibrosis
  • Hydrocephalus

Doubling Dose Concept

• Doubling the dose doubles how much offspring are affected by ionizing radiation (background)
• The dose that causes the number of spontaneous mutations in one generation to double includes:
  • 7% offspring with mutations in absence of radiation
  • 1.56 Sv estimated radiation dose in sieverts
  • 14% offspring with mutation after receiving a doubling equivalent dose