Journal article
Pretreatment with valproic acid, a histone deacetylase inhibitor, enhances the sensitivity of the peripheral blood micronucleus assay in rodents
Mutation research. Genetic toxicology and environmental mutagenesis, Vol.751(1), pp.19-26
02/18/2013
DOI: 10.1016/j.mrgentox.2012.10.009
PMID: 23142536
Abstract
Micronucleus (MN) assay is widely used for the determination of the genotoxic potential of new chemical entities. Improvement in the sensitivity of MN assay will be advantageous for the successful detection of marginally active genotoxins. In the past, several improvements have been made in the automated scoring of micronuclei, while very few attempts have been taken to improve the sensitivity of manual micronuclei detection. The present study aims to validate the effect of valproic acid (VPA) pretreatment on the sensitivity of peripheral blood micronucleus (PBMN) assay using cyclophosphamide (CP, 50 mg/kg), methotrexate (MIX, 20 mg/kg) and zidovudine (AZT, 400 mg/kg) in rodents. However, to find out the optimum VPA pretreatment time as well as to detect the effect of species and age difference, separate experiments were conducted on young Swiss albino mice (24-28 days) and Sprague-Dawley rats (21-24 days), in which significant increase in MN induction was observed with 3-day VPA pretreatment in both the species. Based on these results, studies on adult mice were conducted with 3-day VPA pretreatment along with CP or MIX or AZT. The results of the present study clearly demonstrate that the 3-day VPA pretreatment significantly enhances the sensitivity of PBMN assay in peripheral blood (PB) in adult mice. After validation with other standard genotoxins as well as other HDAC (histone deacetylase) inhibitors, this model may be useful for the detection of marginally active DNA damaging agents. (C) 2012 Elsevier B.V. All rights reserved.
Details
- Title: Subtitle
- Pretreatment with valproic acid, a histone deacetylase inhibitor, enhances the sensitivity of the peripheral blood micronucleus assay in rodents
- Creators
- T. Ahmad - National Institute of Pharmaceutical Education and ResearchK. Shekh - National Institute of Pharmaceutical Education and ResearchS. Khan - National Institute of Pharmaceutical Education and ResearchA. Vikram - National Institute of Pharmaceutical Education and ResearchL. Yadav - National Institute of Pharmaceutical Education and ResearchC. V. Parekh - National Institute of Pharmaceutical Education and ResearchG. B. Jena - National Institute of Pharmaceutical Education and Research
- Resource Type
- Journal article
- Publication Details
- Mutation research. Genetic toxicology and environmental mutagenesis, Vol.751(1), pp.19-26
- Publisher
- Elsevier
- DOI
- 10.1016/j.mrgentox.2012.10.009
- PMID
- 23142536
- ISSN
- 1383-5718
- eISSN
- 1879-3592
- Number of pages
- 8
- Grant note
- National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, India
- Language
- English
- Date published
- 02/18/2013
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359580002771
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