Modelling the frequencies of chromosomal aberrations in peripheral lymphocytes of patients undergoing radiotherapy

Recently, several attempts have been undertaken to correlate in vitro calibration curves with observed frequencies of chromosomal aberrations and micronuclei in lymphocytes of patients undergoing radiotherapy. The aim of such correlations is the search for a biological method to reconstruct the dose received during radiotherapy. While the in vitro dose-response curves are linear-quadratic, the observed in vivo relationship is usually linear and there is some controversy as to the nature of the observed linearity. We have, therefore, constructed a model to calculate the frequencies and distributions of chromosomal aberrations in lymphocytes of patients undergoing conventional radiotherapy. The model assumes that each fraction of radiation induces a certain number of Poisson-distributed aberrations in the irradiated blood volume. In addition, a simplified assumption is made that lymphocytes flow freely inside the body of the patient and no elimination of cells occurs. The model yields linear dose response curves. The steepness of the curves increases with increasing size of irradiated block of tissue (referred to as irradiated volume) and increasing dose per fraction. The distributions of aberrations become increasingly overdispersed with increasing dose per fraction but are independent of the number of radiation fractions. The modelled dose-response curves agree well with the majority of published experimental results. Given the simple assumptions made, this indicates that cell elimination, which occurs during radiotherapy does not bias the results obtained experimentally. The linearity of the dose response-curve results from the fractionated irradiation. Hence, great care should be applied when attempting to use standard, linear-quadratic calibration curves to estimate the doses received by patients during radiotherapy.