Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia

摘要: Chromosomal translocations involving the MLL gene occur in about 80% of infant leukemia. In search for possible agents inducing leukemia, we identified bioflavonoids, natural substances food as well dietary supplements, that cause site-specific DNA cleavage breakpoint cluster region (BCR) vivo. The BCR was shown primary progenitor hematopoietic cells from healthy newborns and adults cell lines; it colocalized with site induced by chemotherapeutic agents, such etoposide (VP16) doxorubicin (Dox). Both vivo additional vitro experiments demonstrated topoisomerase II (topo II) target bioflavonoids similar to VP16 Dox. Based on 20 tested, a common structure essential topo II-induced cleavage. Reversibility religation bioflavonoid VP16-induced site. Our observations support two-stage model cellular processing inhibitors: first reversible stage results repair, but also rarely chromosome translocations; whereas second, nonreversible leads death because an accumulation damage. These suggest maternal ingestion may induce breaks potentially utero leading early childhood