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FLOW CYTOMETRIC DETECTION OF ABNORMAL FETAL ERYTHROPOIESIS: APPLICATION TO 5-FLUOROURACIL-INDUCED ANEMIA
Citation:
Zucker, R., K. Elstein, D. Shuey, AND J. Rogers. FLOW CYTOMETRIC DETECTION OF ABNORMAL FETAL ERYTHROPOIESIS: APPLICATION TO 5-FLUOROURACIL-INDUCED ANEMIA. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/300, 1995.
Description:
Previously, we observed that administration of 20-40 mg/kg 5-fluorouracil (5-FU) to pregnant rats on gestational day (GD) 14 produced fetal anemia on GD 16-17, as evidenced by dose-dependent decreases in the cell counts, hematocrit, and hemoglobin content of fetal blood obtained by cardiac puncture. n this study, we used flow cytometric analysis to further characterize the 5-FU-induced anemia by analyzing the cell size, nucleic acid content, and percentage of circulating liver-derived reticulocytes relative to yolk-sac-derived erythroblasts. n addition, we sought to determine whether samples obtained by exsanguination would give results comparable to those obtained by cardiac puncture. orty-eight hours after 5-FU administration, both cardiac and peripheral blood samples exhibited a dose-dependent decrease in the relative percentage of reticulocytes, indicating a reduced rate of reticulocyte release from the fetal liver. oreover, at 30 and 40 mg/kg, reticulocytes exhibited increased size and reduced RNA content on GD 16, but elevated RNA content (indicative of premature release) by GD 18. hese data suggest that 5-FU reversibly inhibits both erythroid cell proliferation and RNA synthesis, resulting in an anemia that triggers compensatory release of immature reticulocytes. hus by using flow cytometry to analyze fetal blood, we were able to detect and characterize 5-FU-induced perturbations of erythropoiesis. n so doing, flow cytometry afforded the advantages of rapid determination of individual cell type, size, and RNA content, and the ability to exclude contaminating maternal erythrocytes from analysis, thereby eliminating the need to acquire samples through the difficult and time-consuming technique of cardiac puncture.