PMID- 7541166
OWN - NLM
STAT- MEDLINE
DCOM- 19950728
LR  - 20131121
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 51
IP  - 1
DP  - 1995 Jan
TI  - Flow cytometric detection of abnormal fetal erythropoiesis: application to 
      5-fluorouracil-induced anemia.
PG  - 37-44
AB  - We sought to determine whether flow cytometric analysis of circulating fetal 
      blood cells could be used to rapidly detect perturbations of fetal 
      erythropoiesis. In addition, we wanted to determine whether this approach would 
      allow sample collection by exsanguination instead of fetal cardiac puncture, a 
      difficult technique used to prevent contamination of samples with maternal 
      erythrocytes. To monitor fetal erythropoiesis from gestational day (GD) 14-20, we 
      analyzed the cell size, RNA content, and percentage of circulating liver-derived 
      reticulocytes relative to yolk-sac-derived erythroblasts. As a model toxicant, we 
      chose 5-fluorouracil (5-FU), since we previously observed that maternal 
      administration at 20-40 mg/kg 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. 
      We report herein that 48 hr after maternal 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. Moreover, 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. These data suggest that 5-FU inhibits 
      both erythroid cell proliferation and RNA synthesis reversibly, resulting in an 
      anemia that triggers compensatory release of immature reticulocytes.(ABSTRACT 
      TRUNCATED AT 250 WORDS)
FAU - Zucker, R M
AU  - Zucker RM
AD  - Developmental Toxicology Division, U.S. Environmental Protection Agency, Research 
      Triangle Park, North Carolina 27711, USA.
FAU - Elstein, K H
AU  - Elstein KH
FAU - Shuey, D L
AU  - Shuey DL
FAU - Rogers, J M
AU  - Rogers JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 63231-63-0 (RNA)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Anemia/*chemically induced/embryology
MH  - Animals
MH  - Erythrocyte Count
MH  - Erythroid Precursor Cells
MH  - *Erythropoiesis
MH  - Female
MH  - Fetal Blood/*cytology
MH  - Fetal Diseases/blood/*chemically induced
MH  - Fetal Heart
MH  - Flow Cytometry
MH  - Fluorouracil/*toxicity
MH  - Gestational Age
MH  - *Hematopoiesis, Extramedullary
MH  - Pregnancy
MH  - Pregnancy Complications, Hematologic/*chemically induced
MH  - Punctures
MH  - RNA/blood
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reticulocytes
MH  - Yolk Sac
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1002/tera.1420510106 [doi]
PST - ppublish
SO  - Teratology. 1995 Jan;51(1):37-44. doi: 10.1002/tera.1420510106.