Enhanced frequency of sister chromatid exchanges induced by diepoxybutane is specific characteristic of Fanconi anemia cellular phenotype

Fanconi anemia (FA) is a rare genetically heterogeneous disease characterized by developmental abnormalities, progressive bone marrow failure, and cancer susceptibility. We examined spontaneous, diepoxybutane (DEB)- induced and radiation-induced sister chromatid exchanges (SCEs) in wholeblood lymphocyte cultures of bone marrow failure (BMF) patients including Fanconi anemia, mothers of affected individuals, and healthy controls. The baseline frequency of SCE in FA cells was similar to that observed in controls. However, in response to DEB SCE frequencies in FA patients and their mothers were significantly increased compared to both non-FA BMF families and healthy controls. In response to ionizing radiation, cells displayed increased frequency of SCE, but no differences between FA patients and non-FA BMF patients were seen. Our data confirm and expand previous findings by showing that SCE induced by DEB can be used as an adjunct diagnostic test not only for FA patients, but also for female heterozygous carriers, at least for complementation groups FANCA and FANCD2.