@entity2879 is a @entity4968 that is used to treat a variety of @entity1 @entity5 . Unfortunately, 2-3% of @entity1 treated with @entity2879 develop @entity1778 characterized by 11q23 chromosomal rearrangements. The molecular basis for @entity2879 -induced leukemogenesis is not understood but is associated with enzyme-mediated DNA cleavage. @entity2879 is metabolized by @entity5322 to @entity2879 @entity6153 , which can be further oxidized to etoposide quinone. A @entity5322 variant is associated with a lower risk of @entity2879 -related @entity1778 , suggesting that @entity2879 metabolites may be involved in leukemogenesis. Although @entity2879 acts at the enzyme-DNA interface, several @entity15942 poison topoisomerase II via redox-dependent protein adduction. The effects of etoposide quinone on topoisomerase IIa-mediated DNA cleavage have been examined previously. Although findings suggest that the activity of the @entity3276 is slightly greater than that of @entity2879 , these studies were carried out in the presence of significant levels of reducing agents (which should reduce etoposide quinone to the @entity6153 ). Therefore, we examined the ability of etoposide quinone to poison @entity1 topoisomerase IIa in the absence of reducing agents. Under these conditions, etoposide quinone was    5-fold more active than @entity2879 at inducing enzyme-mediated DNA cleavage. Consistent with other redox-dependent poisons, etoposide quinone inactivated topoisomerase IIa when incubated with the protein prior to DNA and lost activity in the presence of @entity3902 . Unlike @entity2879 , the @entity3276 metabolite did not require @entity855 for maximal activity and induced a high ratio of double-stranded DNA breaks. Our results support the hypothesis that etoposide quinone contributes to @entity2879 -related leukemogenesis.

Etoposide quinone is a redox-dependent XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'human'] @entity3276 :: ('MESH:C004532', 'Chemical') :: ['quinone'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers'] @entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity3902 :: ('MESH:D004229', 'Chemical') :: ['dithiothreitol'] @entity4968 :: ('MESH:D011041', 'Disease') :: ['topoisomerase II poison'] @entity2879 :: ('MESH:D005047', 'Chemical') :: ['etoposide', 'Etoposide'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['treatment-related leukemias', 'leukemias'] @entity15942 :: ('MESH:D011809', 'Chemical') :: ['quinones'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP'] @entity6153 :: ('MESH:C034221', 'Chemical') :: ['catechol']
@entity4968 :: (MESH:D011041,Disease) :: ['topoisomerase II poison']
