The BIANCA model/code of radiation-induced cell death: application to human cells exposed to different radiation types

This paper presents a biophysical model of radiation-induced cell death,
implemented as a Monte Carlo code called BIophysical ANalysis of Cell
death and chromosome Aberrations (BIANCA), based on the assumption
that some chromosome aberrations (dicentrics, rings, and large deletions,
called "lethal aberrations") lead to clonogenic inactivation. In turn,
chromosome aberrations are assumed to derive from clustered, and thus
severe, DNA lesions (called "cluster lesions," or CL) interacting at the
micrometer scale; the CL yield and the threshold distance governing CL
interaction are the only model parameters. After a pilot study on V79
hamster cells exposed to protons and carbon ions, in the present work the
model was extended and applied to AG1522 human cells exposed to
photons, He ions, and heavier ions including carbon and neon. The
agreement with experimental survival data taken from the literature
supported the assumptions. In particular, the inactivation of AG1522 cells
was explained by lethal aberrations not only for X-rays, as already
reported by others, but also for the aforementioned radiation types.
Furthermore, the results are consistent with the hypothesis that the critical
initial lesions leading to cell death are DNA cluster lesions having yields in
the order of similar to 2 CL Gy(-1) cell(-1) at low LET and similar to 20 CL
Gy(-1) cell(-1) at high LET, and that the processing of these lesions is
modulated by proximity effects at the micrometer scale related to
interphase chromatin organization. The model was then applied to
calculate the fraction of inactivated cells, as well as the yields of lethal
aberrations and cluster lesions, as a function of LET; the results showed a
maximum around 130 keV/mu m, and such maximum was much higher for
cluster lesions and lethal aberrations than for cell inactivation.