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Titolo:
Persistence of aneuploid immature/primitive hemopoietic sub-populations inmice 8 months after benzene exposure in vivo
Autore:
Giver, CR; Wong, R; Moore, DH; Pallavicini, MG;
Indirizzi:
Univ Calif San Francisco, Ctr Canc, Dept Lab Med & Radiat Oncol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
fascicolo: 1-2, volume: 491, anno: 2001,
pagine: 127 - 138
SICI:
1383-5718(20010405)491:1-2<127:POAIHS>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-SITU HYBRIDIZATION; MOUSE BONE-MARROW; CYTOGENETICALLY ABERRANT CELLS; PRIMITIVE HEMATOPOIETIC-CELL; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; LONG ARM DELETION; STEM-CELLS; CORN-OIL; HUMAN-LYMPHOCYTES;
Keywords:
aneuploid; leukemia; genotoxins; benzene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Pallavicini, MG Univ Calif San Francisco, Ctr Canc, Dept Lab Med & Radiat Oncol, POB 0808,San Francisco, CA 94143 USA Univ Calif San Francisco POB 0808 San Francisco CA USA 94143
Citazione:
C.R. Giver et al., "Persistence of aneuploid immature/primitive hemopoietic sub-populations inmice 8 months after benzene exposure in vivo", MUT RES-GTE, 491(1-2), 2001, pp. 127-138

Abstract

Benzene (bz) is a common environmental contaminant associated with increased risk of myeloid leukemia. Chronic bz exposure in vivo increases the frequency of aneuploid circulating lymphocytes in humans. However, there is no information about persistence of bz-associated aneuploidy in immature/primitive cells, at risk of leukemic transformation, after bz exposure in vivo. We explored the relationship between the induction and persistence of aneuploidy in primitive hemopoietic cells from mice that received oral doses of bz in vivo. Short- and long-term persistence of aneuploidy were evaluated in immature/primitive sub-populations (Lin(-)c-kit(+)Sca-1(+)), as well as lymphoid and myeloid cells, 6 days and 2-8 months after exposure. Mice receiving bz in a corn oil carrier, or corn oil alone, both have increased aneuploidy frequencies (1-5%, compared to <1% in untreated controls) in all sub-populations. 6 days after exposure. However, unlike bz-induced aneuploidy, corn oil-induced aneusomies are transient, with frequencies returning to background levels in lymphoid and myeloid cells, 9 weeks after exposure. The frequency (5-9%) of aneuploid lymphocytes and myeloid cells is higher at 9 weeks than at 6 days, suggesting that bz disrupts chromosomal segregation in differentiated cells and/or progenitors. About 8 months after bz exposure, the Lin(-)c-kit(+)Sca-1(+) sub-population contains up to 14% aneuploid cells with numerical chromosomal aberrations affecting chromosomes 2 or 11. These data demonstrate that bz induces DNA copy number changes in immature/primitive cells, and that these changes persist for long periods. Although, initial exposures are not leukemogenic, subsequent exposures of cells to genotoxins or oxidative radicals that induce additional genetic hits may increase the risk of transformation. The contribution of bz-induced aneuploidy in immature/primitive cells to leukemogenesis remains to be determined. (C)2001 Published by Elsevier Science B.V.

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Documento generato il 29/03/20 alle ore 15:28:43