Prior bleeding enhances the sensitivity of peripheral blood and bone marrow micronucleus tests in rats

Ajit Vikram; Poduri Ramarao; Gopabandhu Jena

doi:10.1093/mutage/gem015

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Prior bleeding enhances the sensitivity of peripheral blood and bone marrow micronucleus tests in rats

Journal article

Open access

Peer reviewed

Prior bleeding enhances the sensitivity of peripheral blood and bone marrow micronucleus tests in rats

Ajit Vikram, Poduri Ramarao and Gopabandhu Jena

Mutagenesis, Vol.22(4), pp.287-291

07/2007

DOI: 10.1093/mutage/gem015

PMID: 17548865

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Abstract

The rat peripheral blood micronucleus (MN) assay is not considered to be a sufficient biomarker of genotoxin exposure due to the selective elimination of micronucleated cells from peripheral circulation by the spleen. However, several recent reports suggest that peripheral blood reticulocytes of rats may represent a suitable cell population for use in the MN assay. The MN assay in rats with prior bleeding was thus conducted to determine the sensitivity of the bioassay. Hirai et al. reported that prior bleeding enhances the sensitivity of the in vivo MN test in mice. Based on these findings, the rat was used as a model to see the effect of prior bleeding on the sensitivity of the peripheral blood and bone marrow MN assays. In the present experiment, young male Sprague-Dawley (SD) rats ranging in age from 21 to 24 days were used. However, for the comparison of strain-specific induction of MN, Wistar rats were used. The kinetics of MN formation were investigated in adult, young bled and non-bled SD rats treated with cyclophosphamide (CP). For the MN kinetic study, CP was administered intraperitoneally 2 h after bleeding and sampling was done at intervals of 12, 24, 36, 48 and 96 h after chemical administration. Significant increases in MN induction activity in both bone marrow and peripheral blood were observed with prior bleeding. To further validate the influence of prior bleeding in the induction of MN frequency, two other known genotoxins (chlorambucil and mitomycin C) were used. It was concluded that prior bleeding can significantly increase the sensitivity of MN induction in both bone marrow and peripheral blood of rats compared with non-bled animals. Once validated, this model may be suitable for detecting different genotoxins, especially weak and marginally active clastogens.

Animals

Blood Cells - drug effects

Blood Specimen Collection - methods

Bone Marrow Cells - drug effects

Chlorambucil - administration & dosage

Chlorambucil - toxicity

Male

Micronucleus Tests - methods

Micronucleus Tests - statistics & numerical data

Mitomycin - administration & dosage

Mitomycin - toxicity

Mutagens - administration & dosage

Mutagens - toxicity

Rats

Rats, Sprague-Dawley

Rats, Wistar

Reticulocytes - drug effects

Sensitivity and Specificity

Time Factors

Details

Title: Subtitle: Prior bleeding enhances the sensitivity of peripheral blood and bone marrow micronucleus tests in rats
Creators: Ajit Vikram - National Institute of Pharmaceutical Education and Research
Poduri Ramarao - National Institute of Pharmaceutical Education and Research
Gopabandhu Jena - National Institute of Pharmaceutical Education and Research
Resource Type: Journal article
Publication Details: Mutagenesis, Vol.22(4), pp.287-291
DOI: 10.1093/mutage/gem015
PMID: 17548865
ISSN: 0267-8357
eISSN: 1464-3804
Language: English
Date published: 07/2007
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984359803902771

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