Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Short Communications
Ataxia telangiectasia and rad3 related (ATR)-promyelocytic leukemia protein (PML) pathway of the DNA damage response in the brain of rats administered arsenic trioxide
Ryo WatanabeKana UnumaKanako NoritakeTakeshi FunakoshiToshihiko AkiKoichi Uemura
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2017 Volume 30 Issue 4 Pages 333-337


To examine the in vivo responses of promyelocytic leukemia protein (PML) to arsenic, rats (male, 6 weeks old, Sprague Dawley) were administered a single intraperitoneal dose of 5 mg/kg arsenic trioxide (ATO). The protein was examined in the heart, lung, liver, and brain 6 and 48 hours after administration: a significant response of PML was observed in the brain. Oxidative DNA modification was also observed in the brain as revealed by increased immunoreactivity to anti-8-hydroxy-2’-deoxyguanosine (8-OHdG) antibody. In contrast, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) stain reactivity was only slightly increased, suggesting oxidative cellular stress without apoptotic cell death in the ATO-administered rat brain. Among the DNA damage response pathways, the ATR-Chk1 axis was activated, while the ATM-Chk2 axis was not, implying that the PML response is associated with activation of the ATR-Chk1 DNA repair pathway in the brain.

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© 2017 The Japanese Society of Toxicologic Pathology
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