Quantitative relationships between acentric fragments and micronuclei: new models and implications for curve fitting

摘要

Purpose: To examine the phenomena governing the quantitative relationships between acentric fragments and micronuclei and understand which formulas are useful for curve-fitting of experimental data of micronuclei. Materials and methods: A stochastic model, including the phenomena of inclusion, coalescence and culling out, was developed and applied to experimental data. Results: Probabilities for inclusion/exclusion of acentric fragments into daughter nuclei and for coalescence of many fragments into a single micronucleus were found to be not cell type-specific. The biological basis for this result is explained with the lack of DNA damage checkpoints between metaphase (when acentric fragments are scored) and telophase (when micronuclei are formed). The phenomenon of "culling out" cells with high numbers of acentric fragments is also described, along with its proposed biological mechanism. Conclusions: Apart from complex formulas that describe these phenomena, we discuss which simple formulas can best approximate them and when is the case to use them for curve fitting of micronuclei data.