7.3 Biological dosimetry using chromosomal aberrations

Chromosomal aberrations are like radiation's fingerprints on our DNA. They're changes in our chromosomes that happen when we're exposed to radiation. Scientists can count these changes to figure out how much radiation someone's been exposed to.

This method, called biological dosimetry, is super helpful when we don't have other ways to measure radiation exposure. It's used in emergencies, for worker safety, and in long-term health studies. It's a key tool in understanding how radiation affects our bodies.

Biological Dosimetry and its Applications

Concept and Importance of Biological Dosimetry

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• Biological dosimetry measures radiation dose using biological markers in living organisms exposed to ionizing radiation
• Complements physical dosimetry by estimating absorbed dose based on biological effects rather than direct radiation measurements
• Proves particularly useful in scenarios lacking physical dosimeters or during accidental radiation exposure
• Enables retrospective dose estimates, allowing assessment of past radiation exposures
• Supports radiation protection efforts, emergency response to radiation accidents, and long-term health risk assessment of radiation workers
• Plays a crucial role in epidemiological studies by establishing dose-response relationships for various health effects of radiation exposure

Applications in Radiation Protection and Research

• Assesses occupational exposure in radiation workers (nuclear power plant employees, medical radiologists)
• Evaluates accidental exposures in emergency scenarios (nuclear plant accidents, radiological terrorism)
• Supports long-term health studies of populations exposed to radiation (atomic bomb survivors, Chernobyl victims)
• Aids in validating and refining radiation protection standards and guidelines
• Contributes to research on individual radiosensitivity and personalized radiation risk assessment
• Assists in identifying potential cases of radiation exposure in medical triage situations

Chromosomal Aberrations as Biomarkers

Types and Characteristics of Radiation-Induced Chromosomal Aberrations

• Chromosomal aberrations manifest as structural changes in chromosomes induced by ionizing radiation
• Frequency of chromosomal aberrations in peripheral blood lymphocytes correlates with absorbed radiation dose
• Dicentric chromosomes, characterized by two centromeres, serve as the most specific and sensitive indicators of radiation exposure
• Ring chromosomes form when chromosome ends fuse, creating a circular structure
• Translocations involve the exchange of genetic material between non-homologous chromosomes
• Acentric fragments result from chromosome breakage without centromere attachment
• Inversions occur when a chromosome segment reverses its orientation within the same chromosome

Dose-Response Relationships and Influencing Factors

• Dose-response relationship for chromosomal aberrations typically follows a linear-quadratic model for low-LET radiation
• Linear component (αD) dominates at low doses, while quadratic component (βD²) becomes more significant at higher doses
• Radiation quality affects aberration yield (high-LET radiation produces more complex aberrations)
• Dose rate influences aberration formation (lower dose rates generally produce fewer aberrations per unit dose)
• Individual radiosensitivity factors (genetic predisposition, age, health status) can modify aberration yields
• Persistence of aberrations varies (dicentrics have a half-life of about 1 year, while translocations persist for decades)
• Environmental factors (chemical mutagens, lifestyle choices) may contribute to background aberration levels

Methods for Assessing Chromosomal Aberrations

Dicentric Chromosome Assay (DCA)

• Serves as the gold standard method for assessing chromosomal aberrations in biological dosimetry
• Involves culturing peripheral blood lymphocytes for 48 hours to reach first mitotic division
• Utilizes colcemid to arrest cell division at metaphase
• Prepares metaphase spreads through hypotonic treatment and fixation
• Applies Giemsa staining to visualize chromosomes (appears purple under light microscope)
• Analyzes typically 500-1000 metaphases per sample to detect and quantify dicentric chromosomes
• Enhances detection of specific aberrations using fluorescence in situ hybridization (FISH) techniques (centromere-specific probes)

Alternative and Complementary Techniques

• Cytokinesis-block micronucleus (CBMN) assay measures micronuclei formation as an indicator of chromosomal damage
• Premature chromosome condensation (PCC) allows analysis of chromosomal aberrations without cell division (useful for high-dose exposures)
• Fluorescence in situ hybridization (FISH) enables detection of stable aberrations like translocations for long-term exposure assessment
• Automated microscopy systems and image analysis software increase efficiency and objectivity of aberration scoring
• Next-generation sequencing approaches detect radiation-induced mutations and chromosomal rearrangements at the molecular level
• Electron paramagnetic resonance (EPR) dosimetry of tooth enamel provides an alternative biological dosimetry method for long-term dose assessment

Interpreting Biological Dosimetry Results

Dose Estimation and Calibration

• Estimates dose by comparing observed frequency of chromosomal aberrations to established dose-response calibration curves
• Generates calibration curves through in vitro irradiation of blood samples with known doses of radiation
• Tailors calibration curves to specific radiation qualities (gamma rays, x-rays, neutrons) and dose rates
• Fits yield of dicentric chromosomes to linear-quadratic model: $Y = c + αD + βD²$ (Y: yield, D: dose, c, α, β: coefficients)
• Calculates uncertainties in dose estimates using statistical methods (Poisson distribution for aberration yields)
• Applies 95% confidence limits to provide a range for estimated doses
• Considers time between exposure and blood sampling for accurate dose estimation (lymphocytes with unstable aberrations eliminated over time)

Advanced Analysis and Integration

• Detects and quantifies partial-body exposures by analyzing aberration distribution among cells (Dolphin's method)
• Distinguishes between acute and chronic exposures based on aberration complexity and distribution
• Integrates biological dosimetry results with physical dosimetry and clinical symptoms for comprehensive dose assessment
• Applies Bayesian statistical approaches to combine multiple biodosimetry assays for improved dose estimates
• Utilizes dose reconstruction techniques to estimate organ doses from whole-body biological dosimetry results
• Considers confounding factors (medical procedures, occupational exposures) when interpreting results in non-accident scenarios
• Employs Monte Carlo simulations to assess uncertainties in complex exposure scenarios