Less G(2) arrest in irradiated cells of breast cancer patients than in female controls: a contribution to their enhanced chromosomal radiosensitivity?

Abstract

PURPOSE: To determine if the efficacy of G(2) checkpoint control (measured as the degree of mitotic inhibition) was reduced in breast cancer patients (n=129) compared with healthy controls (n=105) after exposure of lymphocytes to X-rays. We had previously shown that the average level of radiation-induced chromosome damage was higher in G(2) lymphocytes of these patients than in the controls, and it was proposed that this was a marker of low penetrance predisposition to cancer. MATERIALS AND METHODS: Proliferating lymphocytes were X-irradiated (50 cGy) and sampled at 90 min post-irradiation, which was the time of maximum mitotic inhibition of G(2) cells, expressed as the extent of reduction in the mitotic index in irradiated compared with unirradiated cells. RESULTS: Repeated measurements on 28 controls showed that there were reproducible differences in mitotic inhibition between individuals. Inhibition was significantly greater in female than in male controls (p=0.014), but less in patients than in female controls (p=0.009). There was a weak inverse correlation between the extent of inhibition and the amount of chromosome damage in all females (r=-0.15, p=0.043). CONCLUSIONS: The lesser mitotic inhibition in patients than in female controls might contribute to their greater mean G(2) chromosomal radiosensitivity. However, this hypothesis is not easily reconciled with other observations that (1) the significant difference in inhibition between the sexes in controls was not accompanied by any gender difference in radiosensitivity and (2) there was an inverse correlation between inhibition and age in controls, yet no age-related increase in radiosensitivity. There might, therefore, be no causal relationship between G(2) mitotic inhibition and chromosomal radiosensitivity.