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

Autor: Satoko Kakiuchi, Shiro Kondo, Yoshinori Kasahara, Yoshihide Satomi, Mitsuru Kobayshi, Daishiro Miura
Rok vydání: 2006
Předmět:
Zdroj: The Journal of Toxicological Sciences. 31:111-122
ISSN: 1880-3989
0388-1350
DOI: 10.2131/jts.31.111
Popis: 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.
Databáze: OpenAIRE