Chromosomal instability induced by mammography X-rays in primary human fibroblasts from BRCA1 and BRCA2 mutation carriers.
OBJECTIVE
Mammography X-rays are known to induce DNA double-strand breaks (DSB) whose error-free recombinational repair requires the function of the tumour repressor genes BRCA1 (breast-cancer-associated gene 1) and BRCA2 (breast-cancer-associated gene 2). Since un- or misrepaired DSB lead to chromosomal anomalies which may promote the development of breast cancer, we have studied the potential of mammography X-rays for immediate and delayed induction of chromosomal anomalies in human primary fibroblasts from BRCA1 and BRCA2 mutation carriers.


METHODS
Primary human fibroblasts from three BRCA1, three BRCA2 mutation carriers, one BRCA2-deficient fanconi anemia (FA) patient and three normal individuals were exposed to various doses of mammography X-rays. Chromosomal anomalies at first mitosis and at several population doublings post-irradiation were assayed (Giemsa staining and Fish [fluorescence in situ hybridization]).


RESULTS
No effect of the BRCA mutation status was observed on survival curves after exposure to mammography X-rays and on the dose-dependent increase of chromosomal anomalies at first mitosis post-irradiation. In contrast, several population doublings after exposure to a low dose of only 0.5 Gy chromosomal instability, manifested as gross chromosomal rearrangements and aneuploidy, had developed in BRCA2-deficient FA fibroblasts and in some - but not all - BRCA heterozygous fibroblasts.


CONCLUSIONS
Low doses of mammography X-rays have the potential to induce chromosomal instability in fibroblasts from BRCA mutation carriers: Cells exhibit gross chromosomal rearrangements and aneuploidy similar to those observed in breast cancer cells. These results suggest that for women carrying a BRCA mutation early and frequent screening with mammography X-rays may not be the method of choice to detect breast cancer.
Department of Nuclear Medicine, University of Göttingen, Göttingen, Germany.
Marlis
M
Frankenberg-Schwager
Anke
A
Gregus
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D002478:Cells, Cultured; D043171:Chromosomal Instability / Q000235:genetics* / Q000528:radiation effects*; D005260:Female; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D008327:Mammography; D009154:Mutation / Q000235:genetics; D011829:Radiation Dosage; D014965:X-Rays
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human