Less G2 arrest in irradiated cells of breast cancer patients than in female controls:: a contribution to their enhanced chromosomal radiosensitivity?

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.