Chromosomal radiosensitivity in lymphocytes of breast cancer patients with a family history of breast cancer.

A. Baeyens MS a, H. Thierens PhD a, K. Claes MS b, L. Messiaen PhD b, L. de Ridder MD, PhD aand A. Vral PhD a

aDepartment of Anatomy, Embryology, Histology and Medical Physics b Department of Medical Genetics University of Gent, Belgium.

Aim: to investigate chromosomal radiosensitivity in a selected group of breast cancer patients. Methods: the G2 assay and G0-micronucleus assay were performed on blood samples taken from breast cancer patients that were selected according to following criteria: 1) patients with 3 relatives in first degree also with breast cancer or 2) patients with at least 2 relatives in first or second degree where breast cancer is detected before the age of 45. Blood samples of healthy women served as control. For the G2-assay peripheral blood lymphocytes were irradiated with a dose of 0.4 Gy 60Co gamma-rays after 71h incubation in a CO2 incubator at 37°C. At 30 min post-irradiation colcemid was added and 60 min later the cultures were harvested and chromatid breaks were analysed in 50 well spread metaphases. For the MN-assay blood lymphocytes were exposed to 3.5Gy 60Co gamma-rays at a high dose rate (HDR) or low dose rate (LDR) and immediately stimulated with PHA. 24h later cytochalasine B was added and 72h post-irradiation the cultures were arrested. Micronuclei were scored in 1000 binucleate cells. Results: our data show that the mean radiation induced yield of G2 chromatid breaks and G0 micronuclei in breast cancer patients with a family history was significantly higher compared to the mean yield obtained in a population of healthy women. Taking into account the 90th percentile as the cut-off value to determine radiosensitivity 58% of the patients were radiosensitive with the LDR MN assay, 40% with the HDR-MN assay and 40% with the G2 assay. Conclusions: our results support the view that enhanced chromosomal radiosensitivity of peripheral blood lymphocytes is associated with breast cancer predisposition and suggest that genes involved in the processing of radiation induced DNA damage may be breast cancer-predisposing genes of low penetrance.

KEY WORDS: micronuclei, G2 chromatid breaks, gamma-irradiation, blood samples.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Familial and Hereditary Cancer.