PMID- 16956662
OWN - NLM
STAT- MEDLINE
DCOM- 20071031
LR  - 20191210
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 28
IP  - 4
DP  - 2007 Jul
TI  - The evaluation of early embryonic neurogenesis after exposure to the genotoxic 
      agent 5-bromo-2'-deoxyuridine in mice.
PG  - 780-9
AB  - Developmental neurotoxicity (DNT) is an important issue in children's health. 
      Neurogenesis occurs throughout the early fetal to the postnatal period. The 
      proliferation of embryonic stem cells can be a target for toxicants, especially 
      genotoxic compounds. 5-Bromo-2'-deoxyuridine (BrdU), a thymidine analogue, has 
      been used as a marker for proliferating cells. However, we reported that prenatal 
      BrdU exposure induced behavioral abnormalities such as hyperactivity in rat and 
      mouse offspring. In this study, to further clarify the toxic effect of BrdU on 
      the early neurogenesis and to examine the usefulness of the evaluation of this 
      process in DNT, C57BL/6 mice were exposed to 100 mg/kg of BrdU once on 
      gestational day (GD) 9 or 11, and serial sections from a wide variety of areas of 
      the embryonic brains 24 h after the exposure were examined. BrdU exposure on GD11 
      induced cell death in some specific areas, such as the neocortex and striatum, 
      but not in the substantia nigra, raphe and pons, even though BrdU was 
      incorporated into those cells. BrdU decreased the number of cells positive for 
      phosphorylated histone 3 (phospho-histone 3), a marker for proliferating cells at 
      metaphase of mitosis, in the cortex, mammillary body and cerebellum, suggesting 
      that BrdU affected the proliferation of neural stem cells. Exposure on GD9 did 
      not induce cell death in the fetal brain. These results indicate that BrdU 
      actually impaired the early neurogenesis, supporting the postnatal results, and 
      demonstrated that embryonic neurogenesis has heterogeneous sensitivity to the 
      genotoxic agents BrdU that differs according to the area and developmental stage. 
      The evaluation of events in early neurogenesis such as the proliferation of 
      neural stem cells shortly after chemical exposure will be one of the valuable 
      endpoints for studying postnatal neurodevelopmental disorders.
FAU - Kuwagata, Makiko
AU  - Kuwagata M
AD  - Hatano Research Institute, FDSC, Hadano, Kanagawa, Japan. kuwagata.m@fdsc.or.jp
FAU - Ogawa, Tetsuo
AU  - Ogawa T
FAU - Nagata, Tomoko
AU  - Nagata T
FAU - Shioda, Seiji
AU  - Shioda S
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060801
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*toxicity
MH  - Bromodeoxyuridine/metabolism/*toxicity
MH  - Cell Death/drug effects
MH  - Cell Proliferation/drug effects
MH  - Embryo, Mammalian
MH  - Female
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/*drug effects
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects/chemically induced/pathology/physiopathology
MH  - Stem Cells/drug effects/physiology
EDAT- 2006/09/08 09:00
MHDA- 2007/11/01 09:00
CRDT- 2006/09/08 09:00
PHST- 2006/02/03 00:00 [received]
PHST- 2006/07/25 00:00 [revised]
PHST- 2006/07/26 00:00 [accepted]
PHST- 2006/09/08 09:00 [pubmed]
PHST- 2007/11/01 09:00 [medline]
PHST- 2006/09/08 09:00 [entrez]
AID - S0161-813X(06)00190-2 [pii]
AID - 10.1016/j.neuro.2006.07.017 [doi]
PST - ppublish
SO  - Neurotoxicology. 2007 Jul;28(4):780-9. doi: 10.1016/j.neuro.2006.07.017. Epub 
      2006 Aug 1.