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Titolo:
Neural precursor cell apoptosis and glial tumorigenesis following transplacental ethyl-nitrosourea exposure
Autore:
Leonard, JR; DSa, C; Klocke, BJ; Roth, KA;
Indirizzi:
Washington Univ, Sch Med, Dept Pathol & Immunol, Div Neuropathol, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 Neuropathol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 Neurol Surg, St Louis, MO 63110 USA
Titolo Testata:
ONCOGENE
fascicolo: 57, volume: 20, anno: 2001,
pagine: 8281 - 8286
SICI:
0950-9232(200112)20:57<8281:NPCAAG>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; CHEMOTHERAPY-INDUCED APOPTOSIS; X-DEFICIENT MICE; BCL-X; BRAIN-TUMORS; STEM-CELLS; DEATH; NEURONS; P53; CASPASE-3;
Keywords:
p53; astrocytoma; Bcl-X-L; programmed cell death;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Roth, KA Washington Univ, Sch Med, Dept Pathol & Immunol, Div Neuropathol,660 S Euclid Ave,Box 8118, St Louis, MO 63110 USA Washington Univ 660 S Euclid Ave,Box 8118 St Louis MO USA 63110 A
Citazione:
J.R. Leonard et al., "Neural precursor cell apoptosis and glial tumorigenesis following transplacental ethyl-nitrosourea exposure", ONCOGENE, 20(57), 2001, pp. 8281-8286

Abstract

Neural precursor cells (NPCs) populate the embryonic ventricular zone and persist in the subependymal zone of the adult brain. We hypothesized that hereditary and/or acquired mutations in apoptosis-associated genes, such as p53 and caspases, may protect NPCs from DNA damage-induced death and predispose them to subsequent neoplastic transformation. To test this hypothesis,we exposed NPCs from wild-type and targeted gene-disrupted mouse embryos (p53, caspase-9, caspase-3, and bax mutants) to ethyl-nitrosourea (ENU), a known DNA mutagen and neural carcinogen, and measured NPC viability. We found that ENU produced caspase-3 activation and apoptotic NPC death 6-24 h after administration both in vivo and in vitro. This effect was critically dependent on p53 and caspase-9 expression. The long-term effect of intrauterine ENU exposure was examined in control and p53-deficient mice. High grade glial tumors were found in 60% of p53(-/-) young adult mice exposed to ENU on gestational day 12.5 but not in p53(+/-) or P53(+/+) littermates or in untreated p53-deficient mice. All the tumors were located supratentorially and possessed strong immunoreactivity for glial fibrillary acidic protein andthe anti-apoptotic molecule Bcl-X-L. These results suggest that intrauterine exposure of NPCs to certain DNA damaging agents may synergistically interact with specific genetic abnormalities (e.g. p53 deficiency) to produce glial neoplasms in the adult brain.

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Documento generato il 15/07/20 alle ore 08:43:24