Journal article
Evaluation of multi-organ DNA damage by comet assay from 28 days repeated dose oral toxicity test in mice: A practical approach for test integration in regulatory toxicity testing
Regulatory toxicology and pharmacology, Vol.58(1), pp.145-154
10/01/2010
DOI: 10.1016/j.yrtph.2010.05.004
PMID: 20488216
Abstract
The use of comet assay is not new in the evaluation of genotoxic potential of different agents; however, its broad use in product safety for regulatory testing is a relatively new approach. The present study was aimed to integrate genotoxicity tests (micronucleus and comet assay) in 28 days repeated dose oral toxicity of methotrexate (MTX) in mice. MTX was administered at the dose of 0.5, 1 and 2 mg/kg per oral repeatedly for 28 days in mice. The endpoints of evaluation for routine toxicity testing included body weight, organ weight, food intake, water intake, hematology and histology, while for the genotoxicity testing micronucleus and comet assay were used. There were no significant changes in food intake, water intake and organ weight; however, the body weight significantly decreased at the highest dose of MIX treatment as compared to control group. Histological data revealed the morphological alterations in the liver and lung cells at the highest dose of MTX treatment. Micronucleus assay results indicated that the highest dose of MIX led to significant increase in MNERT5/1000ERTs (P < 0.001) as compared to control group. Further, percentage of reticulocytes (% RETs) was significantly decreased at the highest dose of MTX as compared to control group. Comet assay results indicate significant DNA damage in different organs induced by MIX as compared to control group. The results of the present study successfully demonstrates the integration of genotoxicity tests using comet and micronucleus assay in 28 days repeated dose oral toxicity test. Integration of genotoxicity test with routine toxicity test would reduce the cost of additional animals, test item and provide further information at an early stage of product development. (C) 2010 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Evaluation of multi-organ DNA damage by comet assay from 28 days repeated dose oral toxicity test in mice: A practical approach for test integration in regulatory toxicity testing
- Creators
- S. Kushwaha - Natl Inst Pharmaceut Educ & Res, Dept Pharmacol & Toxicol, Sas Nagar 160062, Punjab, IndiaD. N. Tripathi - National Institute of Pharmaceutical Education and ResearchA. Vikram - National Institute of Pharmaceutical Education and ResearchP. Ramarao - National Institute of Pharmaceutical Education and ResearchG. B. Jena - National Institute of Pharmaceutical Education and Research
- Resource Type
- Journal article
- Publication Details
- Regulatory toxicology and pharmacology, Vol.58(1), pp.145-154
- Publisher
- Elsevier
- DOI
- 10.1016/j.yrtph.2010.05.004
- PMID
- 20488216
- ISSN
- 0273-2300
- eISSN
- 1096-0295
- Number of pages
- 10
- Grant note
- National Institute of Pharmaceutical Education and Research (NIPER)
- Language
- English
- Date published
- 10/01/2010
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359591802771
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