Chromosomal biodosimetry by unfolding a mixed Poisson distribution: a generalized model

Abstract

Purpose: The current chromosomal biodosimetry system is practically limited to the estimation of equivalent whole-body dose in the low or moderate dose range. To circumvent this problem, a new dosimetry system was developed which was effective over a wide dose range and dose gradient.

Materials and methods: In order to establish a quantitative formalism of a comprehensive dose-response kinetics, chromosome aberration frequencies were studied in human peripheral blood lymphocytes irradiated in vitro with gamma-rays in a dose range of 0.01-50Gy. Using the dose-yield relationship thus established, a new model of biodosimetry was developed which involved unfolding the chromosome aberration distribution into a mixed Poisson distribution and thence into a dose-distribution profile. The model was then tested with chromosome aberration data in lymphocytes irradiated in vitro, simulated partial body irradiation, accidental radiation exposure, therapeutic local irradiation and protracted exposure by internal deposit of Thorotrast.

Results: The dose-yield relations over a wide dose range fit satisfactorily a multiparametric dose-response curve, which included the first approximation kinetics of linear-quadratic dose-response and its distortion by mutual interference among multiple breaks on a chromosome arm. The unfolding strategy using these dose-response kinetics was successfully applied to the various types of radiation exposures; the reconstructed dose profile showing a sharp unimodal peak for moderate or high doses of gamma-rays in vitro irradiation, broadening for high-linear energy transfer radiation, discrimination of doses in the mixed culture of irradiated and unirradiated blood, and reasonable dose distribution for the in vivo exposures.

Conclusion: A novel biodosimetry system was developed. The system is innovative in that it provides information not only on the macroscopic dose inhomogeneity, but also on the microscopic spectrum of doses stemming from the variability of energy transfer by charged particles as well as the multiple ionization events to which the target cell nucleus is exposed.