Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment

LIFE SCIENCES

卷:93

Article

Krynetskiy, Evgeny¹  Krynetskaia, Natalia¹  Rihawi, Diana¹  Wieczerzak, Katarzyna²  Ciummo, Victoria²  Walker, Ellen¹ 

[1] Temple Univ, Sch Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19140 USA

[2] Temple Univ, Coll Sci & Technol, Philadelphia, PA 19140 USA

关键词: Acquisition;    Autoshaping;    Chemotherapy;    Cognition;    DNA damage;    5-Fluorouracil;   

DOI  :  10.1016/j.lfs.2013.03.013

来源: Elsevier

【 摘 要 】

Aims: Chemotherapy-associated cognitive impairment often follows cancer chemotherapy. We explored chemotherapy-induced DNA damage in the brain cells of mice treated with 5-fluorouracil (5FU), an antineoplastic agent, to correlate the extent of DNA damage to behavioral functioning in an autoshaping-operant mouse model of chemotherapy-induced learning and memory deficits (Foley et al., 2008). Main methods: Male, Swiss-Webster mice were injected once with saline or 75 mg/kg 5FU at 0, 12, and 24 h and weighed every 24 h. Twenty-four h after the last injection, the mice were tested in a two-day acquisition and the retention of a novel response task for food reinforcement. Murine brain cells were analyzed for the presence of single- and double-strand DNA breaks by the single cell gel electrophoresis assay (the Comet assay). Key findings: We detected significant differences (p < 0.0001) for all DNA damage characteristics (DNA comet tail shape, migration pattern, tail moment and olive moments) between control mice cohort and 5FU-treated mice cohort: tail length - 119 vs. 153; tail moment - 101 vs. 136; olive moment - 60 vs. 82, correspondingly. We found a positive correlation between increased response rates (r = 0.52, p < 0.05) and increased rate of errors (r = 0.51, p < 0.05), and DNA damage on day 1. For all 15 mice (saline-treated and 5FU-treated mice), we found negative correlations between DNA damage and weight (r = -0.75, p < 0.02). Significance: Our results indicate that chemotherapy-induced DNA damage changes the physiological status of the brain cells and may provide insights to the mechanisms for cognitive impairment after cancer chemotherapy. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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