ArticleBiochemical and biophysical research communications2010
Genistein induces topoisomerase IIbeta- and proteasome-mediated DNA sequence rearrangements: Implications in infant leukemia.
Article in Biochemical and biophysical research communications, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 48 citations in OpenAlex.
- Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
- Targeting STAT proteins via computational analysis in colorectal cancer.Molecular and cellular biochemistry · 2021Article
- Bioflavonoids cause DNA double-strand breaks and chromosomal translocations through topoisomerase II-dependent and -independent mechanisms.Mutation research. Genetic toxicology and environmental mutagenesis · 2020Article
- 6,6'-Dihydroxythiobinupharidine as a poison of human type II topoisomerases.Bioorganic & medicinal chemistry letters · 2019Article
- Bioflavonoids promote stable translocations between MLL-AF9 breakpoint cluster regions independent of normal chromosomal context: Model system to screen environmental risks.Environmental and molecular mutagenesis · 2019Article
- The cardioprotective effect of dexrazoxane (Cardioxane) is consistent with sequestration of poly(ADP-ribose) by self-assembly and not depletion of topoisomerase 2B.Ecancermedicalscience · 2018Article
- Top2b is involved in the formation of outer segment and synapse during late-stage photoreceptor differentiation by controlling key genes of photoreceptor transcriptional regulatory network.Journal of neuroscience research · 2017Article
- Topoisomerase-mediated chromosomal break repair: an emerging player in many games.Nature reviews. Cancer · 2015Review
- In vitro action of flavonoids in the canine malignant histiocytic cell line DH82.Molecules (Basel, Switzerland) · 2013Article
- Long-term effects of chromatin remodeling and DNA damage in stem cells induced by environmental and dietary agents.Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer · 2013Review
- Mechanism of generation of therapy related leukemia in response to anti-topoisomerase II agents.International journal of environmental research and public health · 2012Review
- Early inhibitors of human cytomegalovirus: state-of-art and therapeutic perspectives.Pharmacology & therapeutics · 2011Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Genistein is a bioflavonoid enriched in soy products. However, high levels of maternal soy consumption have been linked to the development of infant leukemia ALL and AML. The majority of infant leukemia is linked to mixed lineage leukemia gene (MLL) translocations. Previous studies have implicated topoisomerase II (Top2) in genistein-induced infant leukemia. In order to understand the roles of the two Top2 isozymes in and the molecular mechanism for genistein-induced infant leukemia, we carried out studies in vitro using purified recombinant human Top2 isozymes, as well as studies in cultured mouse myeloid progenitor cells (32Dc13) and Top2beta knockout mouse embryonic fibroblasts (MEFs). First, we showed that genistein efficiently induced both Top2alpha and Top2beta cleavage complexes in the purified system as well as in cultured mouse cells. Second, genistein induced proteasomal degradation of Top2beta in 32Dc13 cells. Third, the genistein-induced DNA double-strand break (DSB) signal, gamma-H2AX, was dependent on the Top2beta isozyme and proteasome activity. Fourth, the requirement for Top2beta and proteasome activity was mirrored in genistein-induced DNA sequence rearrangements, as monitored by a DNA integration assay. Together, our results suggest a model in which genistein-induced Top2beta cleavage complexes are processed by proteasome, leading to the exposure of otherwise Top2beta-concealed DSBs and subsequent chromosome rearrangements, and implicate a major role of Top2beta and proteasome in genistein-induced infant leukemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.