Dietary topoisomerase II-poisons

Abstract

DNA topoisomerases are nuclear enzymes inducing transient breaks in the DNA allowing DNA strands or double helices to pass through each other. The clinically used DNA topoisomerase II-poison etoposide is known to induce DNA double strand breaks leading to chromosomal aberrations and leukemias. Recently, some alarming studies have been published, suggesting that maternal exposure to low doses of dietary topoisomerase II-poisons, including bioflavonoids such as genistein or quercetin, may contribute to the development of infant leukemia: approximately 80% of infants with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) have chromosome translocations involving the MLL (mixed lineage leukemia) gene. It has been shown that antineoplastic chemotherapy with the leukemogenic topoisomerase II-poison etoposide induced identical chromosomal aberrations involving the MLL gene compared to children with infant leukemia. Interestingly, the MLL cleavage sites induced by etoposide colocalized with the cleavage sites observed in infant leukemia. In addition, an almost 10-fold higher risk of infant AML has been reported for mothers consuming relatively high levels of topoisomerase II-poison containing foods. These observations are relevant, since many foods contain topoisomerase II-poisons, predominantly soy and soy products, but also coffee, wine, tea, cocao, as well as some fruits and vegetables. Further studies on the role of dietary topoisomerase II-poisons are urgently required. If the causal relationship between dietary exposure to topoisomerase II-poisons and infant leukemia will be confirmed, care should be taken to reduce exposure to critical foods during pregnancy.