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Titolo:
Species-, sex-, and cell type-specific effects of ochratoxin A and B
Autore:
OBrien, E; Heussner, AH; Dietrich, DR;
Indirizzi:
Univ Konstanz, D-78457 Constance, Germany Univ Konstanz Constance Germany D-78457 tanz, D-78457 Constance, Germany
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 2, volume: 63, anno: 2001,
pagine: 256 - 264
SICI:
1096-6080(200110)63:2<256:SSACTE>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
BALKAN ENDEMIC NEPHROPATHY; BLADDER EPITHELIAL-CELLS; PROXIMAL TUBULE CELLS; HUMAN-BLOOD; PRIMARY CULTURE; KIDNEY; APOPTOSIS; RAT; GROWTH; INDUCTION;
Keywords:
ochratoxin A; nephropathy; renal cancer; uptake; cytostasis; toxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Dietrich, DR Univ Konstanz, Jacob Burckhardtstr 25,POB 5560 X918, D-78457 Constance, Germany Univ Konstanz Jacob Burckhardtstr 25,POB 5560 X918 Constance Germany D-78457
Citazione:
E. O'Brien et al., "Species-, sex-, and cell type-specific effects of ochratoxin A and B", TOXICOL SCI, 63(2), 2001, pp. 256-264

Abstract

The ubiquitous mycotoxin ochratoxin A (OTA) is associated with the development of urothelial tumors and nephropathies in laboratory animals and in humans with stark species and sex differences with respect to susceptibility in disease development. The mechanism of action remains unknown. OTA-mediated disruptions in normal cell-cycle control could be a major constituent ofthe mechanisms underlying both its carcinogenic and nephropathy-inducing activities. Assessment of OTA's toxic effects (sum of antiproliferative, apoptotic, and necrotic effects) in rat and porcine continuous cell lines and in primary cells from humans and pigs of both sexes, have displayed a similar sex- and species-sensitivity rank order to that observed in previous in vivo experiments. Furthermore, these toxic effects were observed at nM concentrations in the presence of serum in vitro, thus closely mimicking the invivo situation. These effects were reversible in all cell types except in human primary epithelial cells of both sexes and did not appear to be primarily dependent on the amount of OTA taken up. Indeed, fibroblasts (NRK-49F)were insensitive to OTA-mediated cell cycle inhibition in spite of accumulating comparable amounts of OTA. The results presented here support the continued use of primary renal epithelial cells for the investigation of the mechanism of OTA-induced carcinogenesis and nephropathy and provide an as-yet preliminary data set that supports the existence of a causal relationshipbetween OTA exposure and human nephropathy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:33:52