RADIATION-INDUCED MICRONUCLEUS INDUCTION IN LYMPHOCYTES IDENTIFIES A HIGH-FREQUENCY OF RADIOSENSITIVE CASES AMONG BREAST-CANCER PATIENTS - A TEST FOR PREDISPOSITION

Enhanced sensitivity to the chromosome-damaging effects of ionizing ra diation is a feature oi many cancer-predisposing conditions, We previo usly showed that 42% of an unselected series of breast cancer patients and 9% of healthy control subjects showed elevated chromosomal radios ensitivity of lymphocytes irradiated in the G(2) phase of the cell cyc le. We suggested that, in addition to the highly penetrant genes BRCA1 and BRCA2 which confer a very high risk of breast cancer and are carr ied by about 5% of all breast cancer patients, there are also low-pene trance predisposing genes carried by a much higher proportion of breas t cancer patients, a view supported by recent epidemiological studies, Ideally, testing for the presence of these putative genes should invo lve the use of simpler methods than the G(2) assay, which requires met aphase analysis of chromosome damage. Here we report on the use of a s imple, rapid micronucleus assay in G(0) lymphocytes exposed to high do se rate (HDR) or low dose rate gamma-irradiation, with delayed mitogen ic stimulation. Good assay reproducibility was obtained, particularly with the HDR protocol, which identified 31% (12 out of 39) of breast c ancer patients compared with 5% (2 out of 42) of healthy controls as h aving elevated radiation sensitivity In the long term, such cytogeneti c assays may have the potential for selecting women for intensive scre ening for breast cancer.