Increased chromosomal radiosensitivity in breast cancer patients: a comparison of two assays

Purpose: It has been shown previously that sensitivity to the induction of chromosome damage by ionizing radiation is, on average, higher in G(2) or G(0) lymphocytes of breast cancer patients than of normal healthy controls. The authors suggested thar elevated chromosomal radiosensitivity may be a marker for breast cancer predisposition. To investigate whether the G(0) micronucleus assay is a true surrogate for the more demanding G(2) metaphase assay, both tests have now been performed on the same blood samples from 80 patients. Methods: For the G(0) micronucleus assay, cells were exposed to 3.5Gy Cs-137 gamma-rays 6 h before mitogenic stimulation, treated with cytochalasin B at 24 h post-stimulation and harvested at 90 h. For the G(2) assay, at 72 h after stimulation cells were given 0.5 Gy X-rays and harvested 90 min later. Results: Previous observations were confirmed, now with much larger numbers of donors, in that approximately 40% of breast cancer patients showed elevated sensitivity in the G(2) assay (135 patients, 105 normals) and 25% in the G(0) assay (130 patients 68 normals). However, there was no correlation between G(2) and G(0) sensitivity for the 80 patients tested (r = -0.001, p = 0.99). Most of the sensitive patients were either G(2) or G(0) sensitive, with only 4% sensitive in both assays. Conclusions: The results suggest that different mechanisms of chromosomal radiosensitivity operate in G(2) and G(0) cells and that, in general, each chromosomally radiosensitive patient is defective in only one such mechanism, possibly via mutation (or polymorphism) of a single gene. Such mutations may confer cancer predisposition, of low penetrance, in a substantial proportion of patients.