The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Regular paper
FLOW CYTOMETRIC ANALYSIS OF ERYTHROPOIETIC ABNORMALITY: CHANGES IN THE CELL MATURITY INDEX OF RETICULOCYTES AND RETIC DISTRIBUTION INDEX ARE USEFUL AS INDICATORS OF ERYTHROPOIETIC TOXICITY IN NON-CLINICAL STUDIES
Satoko KAKIUCHIMitsuru KOBAYSHIYoshihide SATOMIDaishiro MIURAYoshinori KASAHARAShiro KONDO
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JOURNAL FREE ACCESS

2006 Volume 31 Issue 2 Pages 111-122

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Abstract

We performed a flow cytometric (FCM) analysis of the maturity of reticulocytes using peripheral blood obtained from rats administered 5-fluorouracil (5-FU) at 10, 50 and 100 mg/kg or acethylphenyl hydrazine (APHZ) at 1 and 3 mg/kg to clarify whether the FCM method is useful for assessing toxicity. In the 5-FU-administered rats, a decrease and recovery of the immature reticulocyte fraction (Cell Maturity Index, CMI; Retic Distribution Index, RDI) was observed more rapidly (several days prior to changes in the reticulocyte ratio), and sensitively regarding dose-dependency (clear changes were observed at 10 mg/kg, whereas the reticulocyte ratio was only slightly affected). In addition, there was good agreement between the microscopic results obtained by counting Heilmyer's reticulocyte maturation groups, especially for type I and II, and CMI/RDI assessed by the FCM method after the administration of 50 and 100 mg/kg of 5-FU, the dose at which clear changes were obtained with the microscopic method. In the APHZ-administered rats, a dose-dependent increase in CMI/RDI coinciding with the enhancement of reticulocyte production was observed. The results suggested that the automated FCM method could be a useful and valuable tool to assess and predict impairments of erythropoiesis, especially for CMI and RDI, and could help in the diagnosis of hematological disorders in experimental animals.

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© 2006 The Japanese Society of Toxicology
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