Alcohol exposure alters cell cycle and apoptotic events during early neurulation

Bruce Anthony, Feng Zhou, Tetsuo Ogawa, Charles R. Goodlett, Joseph Ruiz

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Fetal alcohol exposure causes growth deficits, microencephaly, and neurological abnormalities. Although the effects of alcohol on developmental delay and growth-related deficits have been hypothesized, little is understood about how alcohol alters, in particular, the cyclin pathway within the cell cycle, which is critical to proliferation and apoptotic control. In this study, we examined cell cycle proteins pertinent to the G1-S phase transition and apoptosis, to determine if cell cycle misregulation can be attributed to apoptotic induction and growth defects. Methods: We examined cell cycle regulation during G1 and S-phase, and DNA fragmentation damage, using E14 dorsal root ganglia neural stem cells (DRG-NC), and cultured mouse embryos exposed to 200 and 400 mg/dl ethanol. Results: Alcohol-exposed DRG-NC demonstrated a dose-dependent increase in cells expressing increased cyclin D1 protein, and increased DNA fragmentation. Western blot analysis, using embryos, demonstrated an overexpression of cyclin D1, D2, and E2F1, key G1 to S-phase cell cycle regulatory components, and increases in p53, linking the cell cycle and apoptotic pathways. Bromodeoxyuridine incorporation indicated reduced DNA synthesis and growth in several embryonic regions. Propidium iodide staining demonstrated decreases in DNA content and increases in DNA fragmentation in several embryonic tissues. Conclusions: This study indicated that retarded growth of DRG-NC and embryos, induced by alcohol, is associated with altered expression of cell cycle and apoptotic proteins and concurrent inhibition of proliferation and increased DNA fragmentation. We suggest that alcohol induces an increase in cyclin D1 expression, premature S-phase entry, and disjointed DNA synthesis with increased apoptosis.

Original languageEnglish
Pages (from-to)261-273
Number of pages13
JournalAlcohol and Alcoholism
Volume43
Issue number3
DOIs
StatePublished - May 2008

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Neurulation
Cell Cycle
Cells
Alcohols
DNA Fragmentation
S Phase
Neural Stem Cells
DNA
Cyclin D1
Spinal Ganglia
Stem cells
Growth
Cell Cycle Proteins
Embryonic Structures
G1 Phase
Cyclin D2
Apoptosis
Cyclins
Propidium
Phase Transition

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Alcohol exposure alters cell cycle and apoptotic events during early neurulation. / Anthony, Bruce; Zhou, Feng; Ogawa, Tetsuo; Goodlett, Charles R.; Ruiz, Joseph.

In: Alcohol and Alcoholism, Vol. 43, No. 3, 05.2008, p. 261-273.

Research output: Contribution to journalArticle

Anthony, Bruce ; Zhou, Feng ; Ogawa, Tetsuo ; Goodlett, Charles R. ; Ruiz, Joseph. / Alcohol exposure alters cell cycle and apoptotic events during early neurulation. In: Alcohol and Alcoholism. 2008 ; Vol. 43, No. 3. pp. 261-273.
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