Simultaneous use of erythropoietin and prior bleeding enhances the sensitivity of the peripheral blood micronucleus assay

A. Mughal; A. Vikram; S. Kushwaha; G. B. Jena

doi:10.1093/mutage/geq099

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Simultaneous use of erythropoietin and prior bleeding enhances the sensitivity of the peripheral blood micronucleus assay

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Simultaneous use of erythropoietin and prior bleeding enhances the sensitivity of the peripheral blood micronucleus assay

A. Mughal, A. Vikram, S. Kushwaha and G. B. Jena

Mutagenesis, Vol.26(2), pp.331-338

03/01/2011

DOI: 10.1093/mutage/geq099

PMID: 21078813

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Abstract

Adult rats are generally not considered as a suitable model for the peripheral blood micronucleus (PBMN) assay in regulatory consideration, owing to the splenic removal of the micronucleated cells from circulation. Although prior bleeding (PrB) increases the sensitivity of the PBMN assay in young rats, the volume of bleeding and the associated stress caused are major concerns for its possible use in genotoxicity studies. The present study was aimed to overcome these limitations in using pre-bled young rats in genotoxicity studies. The bleeding volume was reduced by the simultaneous use of erythropoietin (EPO) to increase the sensitivity of PBMN assay. Young Sprague-Dawley (SD, 26 days) rats were used in the study. The kinetics of RETs-to-ERTs ratio was determined in response to EPO (10-3000 IU/kg) or PrB (0.1-1.0 ml) at different time points (0, 6, 12, 24, 36, 48, 72 and 96 h). Injection of EPO (30 IU/kg) and PrB (0.5 ml) led to a significant increase in the MN frequency in the PBMN assay in response to cyclophosphamide and zidovudine. The effect of EPO treatment and/or PrB on cell viability and proliferation in the bone marrow (BM) was examined. The results of the present study clearly demonstrate that the simultaneous use of both EPO and PrB enhances the sensitivity of the PBMN assay in young rats due to increased cellular proliferation in the BM. This may provide a useful experimental model for the evaluation of marginally active genotoxicants.

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Toxicology

Details

Title: Subtitle: Simultaneous use of erythropoietin and prior bleeding enhances the sensitivity of the peripheral blood micronucleus assay
Creators: A. Mughal - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, Punjab-160 062, India
A. Vikram - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, Punjab-160 062, India
S. Kushwaha - NIPER, Dept Pharmacol & Toxicol, Mohali 160062, Punjab, India
G. B. Jena - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, Punjab-160 062, India
Resource Type: Journal article
Publication Details: Mutagenesis, Vol.26(2), pp.331-338
DOI: 10.1093/mutage/geq099
PMID: 21078813
NLM abbreviation: Mutagenesis
ISSN: 0267-8357
eISSN: 1464-3804
Publisher: Oxford Univ Press
Number of pages: 8
Grant note: National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, India
Language: English
Date published: 03/01/2011
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984359770602771

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