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• W2029556036 abstract "Doxorubicin can induce the formation of extra-nuclear bodies during mitosis termed micronuclei but the underlying causes remain unknown. Here, we show that sub-lethal exposure to doxorubicin-induced micronuclei formation in human cancer cells but not in non-tumorigenic cells. Occurrence of micronuclei coincided with stability of DNMT1 upon doxorubicin assault, and DNMT1 was localized to the micronuclei structures. Furthermore, 5-aza-2′-deoxycytidine-mediated DNMT1 depletion or siDNMT1 knock-down attenuated the frequency of doxorubicin-induced micronucleated cells. Human DNMT1−/− cells displayed significantly fewer micronuclei compared to DNMT1+/+ cells when challenged with doxorubicin, providing additional evidence for the involvement of DNMT1 in mediating such chromosomal aberrations. Collectively, our results demonstrate a role for DNMT1 in promoting DNA damage-induced genotoxicity in human cancer cells. DNMT1, recently identified as a candidate for doxorubicin-mediated cytotoxicity, is over-expressed in various cancer cell types. We propose that DNMT1 levels in tumor cells may determine the effectiveness of doxorubicin in chemotherapy." @default.
• W2029556036 created "2016-06-24" @default.
• W2029556036 creator A5041037444 @default.
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• W2029556036 date "2009-05-01" @default.
• W2029556036 modified "2023-09-30" @default.
• W2029556036 title "DNA methyltransferase I is a mediator of doxorubicin-induced genotoxicity in human cancer cells" @default.
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• W2029556036 doi "https://doi.org/10.1016/j.bbrc.2009.03.065" @default.
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