Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Characterization of initiated cells in N-methylnitrosourea-induced carcinogenesis of the CNS in the adult rat
Autore:
Kokkinakis, DM; Watson, ML; Honig, LS; Rushing, EJ; Mickey, BE; Schold, SC;
Indirizzi:
Univ Texas, SW Med Ctr, Dept Neurol Surg, Dallas, TX 75390 USA Univ TexasDallas TX USA 75390 tr, Dept Neurol Surg, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Med Ctr, Dept Pathol, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Med Ctr, Dept Neurol, Dallas, TX 75390 USA Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 st Canc, Pittsburgh, PA 15213 USA
Titolo Testata:
NEURO-ONCOLOGY
fascicolo: 2, volume: 3, anno: 2001,
pagine: 99 - 112
SICI:
1522-8517(200104)3:2<99:COICIN>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; MONOCLONAL-ANTIBODY; MALIGNANT GLIOMA; BRAIN; ETHYLNITROSOUREA; DIFFERENTIATION; TUMORS; MICE; P53;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Kokkinakis, DM Univ Texas, SW Med Ctr, Dept Neurol Surg, 5323 Harry Hines Blvd, Dallas, TX 75390 USA Univ Texas 5323 Harry Hines Blvd Dallas TX USA 75390 90 USA
Citazione:
D.M. Kokkinakis et al., "Characterization of initiated cells in N-methylnitrosourea-induced carcinogenesis of the CNS in the adult rat", NEURO-ONCOL, 3(2), 2001, pp. 99-112

Abstract

Glial tumors may originate from the malignant transformation of multipotent glial progenitor cells, but tools to study malignant transformation leading to gliomas are limited by the lack of biological systems that represent early stages of this disease in adult animals. In order to characterize theinitiated cells that give rise to gliomas, we have employed the N-methylnitrosourea (MNU) model for induction of brain tumors in adult rats (Rushing et al,, 1998), Specifically, we have isolated and cultured transformed (premalignant) cells from normal-appearing brains of rats exposed to MNU for 10weeks and from histologically abnormal brains of rats exposed to MNU for 15 weeks, We compared them with cells cultured from control animals under identical conditions. Cultured cells were classified according to their morphology, immunophenotype, karyotype, proliferation capacity, and tumorigenicity in athymic mice. Cultures from untreated normal rat brains grew as monolayers and had normal karyotypes (42 X,Y), epithelioid morphology, and slow proliferative capacity (doubling time >120 h). In contrast, cultured cells from brains of MNU-exposed animals had karyotypes that ranged from normal to highly aneuploid, Aneuploid lines grew rapidly in multilayers (doubling time <24 h), had differentiated astrocytic or oligodendroglial morphology and immunohistochemical staining profile, and yielded tumors in athymic mice. Initiated cells with minor chromosomal aberrations assumed mixed bipolar or tripolar morphologies in high density cultures, proliferated rapidly, butshowed contact inhibition and failed to induce tumors when injected s.c. in athymic mice, In general, lines showing no evidence of chromosomal aberrations had the most epithelioid morphology, proliferated slowly (doubling time >72 h), and retained strict contact growth inhibition. The presumed undifferentiated glial progenitor cells in culture from either control or MNU-treated rats variably expressed markers such as vimentin, nestin, and NG2 proteoglycan, and they weakly expressed the mature astrocytic or oligodendroglial markers glial fibrillary acidic protein or galactocerbroside, respectively. These cultures differentiated to bipolar-tripolar morphology with concomitant maturation to a GFAP+ or GalC+ phenotype upon exposure to secondary messengers such as dibutyryl-cyclic-AMP and/or growth factors such as basic fibrillary growth factor. Continuous stimulation with these messengers resulted in terminal differentiation and consequent death upon withdrawal ofthe stimulus. These results provide information that could lead to detailed characterization of initiated, premalignant cells in the adult brain and to a better understanding of glial carcinogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 01:22:14