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Tissue selective effects of topoisomerase II inhibitors in vivo

ABSTRACT: One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. In vitro experiments showed that doxorubicin can induce histone eviction as well as DNA damage, while etoposide can only induce DNA damage. Here, we compare the transcription responses of different tissues to doxorubicin or etoposide treatment in vivo. Total RNA from respective tissues in FVB mice 1 day or 6 days post indicated drug treatment were extracted and compared to un-treated mice. Two mice were used for each treatment.

ORGANISM(S): Mus musculus

SUBMITTER: Baoxu Pang

PROVIDER: E-GEOD-33626 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.

Pang Baoxu B Qiao Xiaohang X Janssen Lennert L Velds Arno A Groothuis Tom T Kerkhoven Ron R Nieuwland Marja M Ovaa Huib H Rottenberg Sven S van Tellingen Olaf O Janssen Jeroen J Huijgens Peter P Zwart Wilbert W Neefjes Jacques J

Nature communications 20130101

DNA topoisomerase II inhibitors are a major class of cancer chemotherapeutics, which are thought to eliminate cancer cells by inducing DNA double-strand breaks. Here we identify a novel activity for the anthracycline class of DNA topoisomerase II inhibitors: histone eviction from open chromosomal areas. We show that anthracyclines promote histone eviction irrespective of their ability to induce DNA double-strand breaks. The histone variant H2AX, which is a key component of the DNA damage respons ...[more]

PMID: 23715267

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