Mitochondrial topoisomerase I (top1mt) is a novel limiting factor of doxorubicin cardiotoxicity.

ABSTRACT:

Purpose

Doxorubicin is one of the most effective chemotherapeutic agents. However, up to 30% of the patients treated with doxorubicin suffer from congestive heart failure. The mechanism of doxorubicin cardiotoxicity is likely multifactorial and most importantly, the genetic factors predisposing to doxorubicin cardiotoxicity are unknown. On the basis of the fact that mtDNA lesions and mitochondrial dysfunctions have been found in human hearts exposed to doxorubicin and that mitochondrial topoisomerase 1 (Top1mt) specifically controls mtDNA homeostasis, we hypothesized that Top1mt knockout (KO) mice might exhibit hypersensitivity to doxorubicin.

Experimental design

Wild-type (WT) and KO Top1mt mice were treated once a week with 4 mg/kg doxorubicin for 8 weeks. Heart tissues we

SUBMITTER: Khiati S 

PROVIDER: S-EPMC4167185 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature