PMID- 8278935
OWN - NLM
STAT- MEDLINE
DCOM- 19940207
LR  - 20131121
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 48
IP  - 4
DP  - 1993 Oct
TI  - Effects of developmental stage and tissue type on embryo/fetal DNA distributions 
      and 5-fluorouracil-induced cell-cycle perturbations.
PG  - 355-63
AB  - Cell-cycle analysis of nuclei obtained from the circulating erythroblasts 
      (gestational day [GD] 11-16), livers (GD 14-19), and whole embryos (GD 10-13) or 
      remaining (extrahepatic) tissues (GD 14-16) of rat embryos/fetuses revealed age- 
      and tissue-dependent variations in the relative percentages of cells in the 
      G0/G1, S, and G2/M phases of the cell cycle. With development, the rate of cell 
      proliferation declined resulting in decreases in the relative percentage of 
      S-phase cells and increases in the G0/G1 percentage, while the percentage of 
      G2/M-phase cells remained relatively constant. Comparing tissue cell-cycle 
      profiles during development, erythroblasts exhibited the most rapid age-dependent 
      decline in S-phase percentage (from 75% at GD 11 to 8% by GD 14), 
      embryos/extrahepatic tissues exhibited a more gradual reduction (from 55% at GD 
      10 to 14% by GD 15), while the hepatic isolates exhibited a relatively constant 
      S-phase percentage of approximately 40% from GD 14 to GD 18 before decreasing to 
      23% at GD 19. These age-dependent variations suggest that cell-cycle distribution 
      may be useful in staging embryogenesis and in detecting abnormal development. To 
      determine how these developmental and organ-specific cell-cycle variations affect 
      toxic response, we sampled GD 11-13 embryos 6 hr after maternal administration of 
      a teratogenic dose of 5-fluorouracil (5-FU), a thymidylate synthetase inhibitor 
      that induces S-phase accumulation. The results indicate that, on a relative 
      basis, the amount of induced S-phase accumulation in erythroblasts and whole 
      embryos 6 hr postdosing increased with development.(ABSTRACT TRUNCATED AT 250 
      WORDS)
FAU - Elstein, K H
AU  - Elstein KH
AD  - ManTech Environmental Technology, Inc., Research Triangle Park, North Carolina 
      27709.
FAU - Zucker, R M
AU  - Zucker RM
FAU - Andrews, J E
AU  - Andrews JE
FAU - Ebron-McCoy, M
AU  - Ebron-McCoy M
FAU - Shuey, D L
AU  - Shuey DL
FAU - Rogers, J M
AU  - Rogers JM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 9007-49-2 (DNA)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Animals
MH  - Cell Cycle/*drug effects
MH  - Cell Division/drug effects
MH  - Cell Nucleus/chemistry/drug effects
MH  - DNA/*analysis
MH  - Embryo, Mammalian/*chemistry/cytology/drug effects
MH  - Embryonic and Fetal Development/*drug effects
MH  - Erythroblasts/chemistry
MH  - Fetus/*chemistry/cytology/drug effects
MH  - Fluorouracil/*pharmacology/toxicity
MH  - Gestational Age
MH  - Liver/embryology
MH  - Organ Specificity
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
AID - 10.1002/tera.1420480409 [doi]
PST - ppublish
SO  - Teratology. 1993 Oct;48(4):355-63. doi: 10.1002/tera.1420480409.