کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2595575 | 1562344 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evaluation of the genotoxicity of tamoxifen in the liver and kidney of F344 gpt delta transgenic rat in 3-week and 13-week repeated dose studies
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Transgenic rat gene mutation assays can be used to assess genotoxicity of chemicals in target organs for carcinogenicity. Mutations in transgenes are genetically neutral and accumulate during a treatment period; thus, the assays are suitable for assessment of the genotoxicity risk of chemicals using a repeated-dose treatment paradigm. However, few such studies have been conducted. To examine the utility of the transgenic rat assays in repeated-dose studies, we treated female F344 gpt delta rats with tamoxifen (TAM) at 20 and 40Â mg/kg, or toremifene (TOR) at 40Â mg/kg by gavage daily for 3 weeks. We also fed gpt delta rats with TAM at either 250Â ppm (15.4-17.6Â mg/kg) or 500Â ppm (30.0-32.9Â mg/kg) for 13 weeks. TAM is carcinogenic in the rat liver and TOR is not carcinogenic. TAM administration significantly increased gpt (point mutations) and Spiâ (deletions) mutant frequencies (MFs) in the liver, the target organ of carcinogenesis; MFs were higher after treatment for 13 weeks than after treatment for 3 weeks. The MFs in the kidney did not increase in any of the TAM treatment groups. TOR had no effect on MFs (gpt and Spiâ) in either the liver or the kidney. We conclude that the gpt delta rat assay in the repeated-dose treatment paradigm is sensitive enough to detect gene mutations induced by TAM in the target organ for carcinogenesis. Furthermore, the assay can be integrated into a 13-week dose-finding study for a 2-year cancer bioassay.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 312, 4 October 2013, Pages 56-62
Journal: Toxicology - Volume 312, 4 October 2013, Pages 56-62
نویسندگان
Yuji Kawamura, Hiroyuki Hayashi, Yasushi Kurata, Kazuyuki Hiratsuka, Kenichi Masumura, Takehiko Nohmi,