CAS

CAS simulates radiogenic chromosomal aberrations using a Monte Carlo extension of the random breakage-and-reunion model and FISH-based identification to quantify dicentrics, translocations, rings, insertions, three-way exchanges and other aberrations for comparison of X-rays and alpha particles (238Pu).

Key Features:

• Monte Carlo simulation framework: Extends the random breakage-and-reunion model to accommodate high linear energy transfer (LET) radiation scenarios.
• FISH-based aberration identification: Leverages fluorescence in situ hybridization (FISH) to identify and categorize dicentrics, translocations, rings, insertions and three-way exchanges.
• Adjustable parameters: Two parameters—number of interaction sites per cell nucleus and number of reactive double-strand breaks (DSBs) per gray—control simulation behavior.
• Radiation-specific calibration and validation: Compares simulated outputs with empirical data from human cells exposed to X-rays and alpha particles (238Pu) and matches published data.
• Aberration categories and painted chromosomes: Predicts aberration frequencies for painted chromosomes of varying lengths across 11 categories of simple or complex aberrations.
• Parameter estimates and RBE: Reports optimal interaction sites of approximately 13 for X-ray irradiation and about 25 for alpha-particle exposure and estimates the relative biological effectiveness (RBE) of alpha particles at around 4 for inducing reactive DSBs.
• FISH painting extrapolation: Uses FISH data from one painting pattern to forecast outcomes for other painting patterns or whole-genome staining.
• Numerical damage indicator: Computes the total misrejoining number as a comprehensive metric of chromosomal damage.

Scientific Applications:

• Mechanistic analysis of radiation-induced damage: Models formation and classification of radiation-induced chromosomal aberrations and misrejoining events.
• Radiation quality assessment and RBE estimation: Assesses differences between X-rays and alpha particles (238Pu) and estimates RBE for reactive DSB induction.
• Dose–response and DSB quantification: Predicts aberration frequencies per gray based on the reactive DSBs per gray parameter.
• FISH data translation and whole-genome extrapolation: Translates painted-chromosome FISH results to other painting patterns or whole-genome staining.
• Validation against experimental human cell data: Enables direct comparison between simulated outcomes and published irradiation datasets.

Methodology:

Monte Carlo simulations implementing an extended random breakage-and-reunion model for high-LET scenarios, using adjustable parameters for interaction sites per nucleus and reactive DSBs per gray to predict aberration frequencies, compute total misrejoining number, and compare to empirical human cell data.