Increased levels of mutagen-induced chromosome breakage in Down syndrome children with malignancy

Even though an association between Down syndrome (DS) and malignancies has been established, the mechanism behind this is still unclear. We therefore investigated constitutional chromosomal abnormalities and bleomycin-induced chromosome sensitivity in 12 DS children, 8 DS children with malignancies, and 10 normal controls to explore whether these factors play any role in cancer predisposition. Trisomy 21 was the only constitutional cytogenetic abnormality observed in all the DS children. But there was significant variation between the patients and controls with regard to bleomycin sensitivity. Compared to the normal controls, all the DS patients expressed significantly higher chromosomal breaks per cell (b/c) values indicating sensitivity to bleomycin. Furthermore, DS children with malignancies demonstrated significantly higher b/c values than DS children without malignancies. These results permit us to assume that DS children showing mutagen hypersensitivity may be having defective DNA repair competence and hence may be predisposed to malignancies. (C) Elsevier Science Inc., 1997.