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Titolo:
ALTERNATIVE TESTING SYSTEMS FOR EVALUATING NONCARCINOGENIC, HEMATOLOGIC TOXICITY
Autore:
PARCHMENT RE;
Indirizzi:
WAYNE STATE UNIV,HARPER HOSP,DIV HEMATOL ONCOL,3990 JOHN R ST DETROITMI 48202 WAYNE STATE UNIV,KARMANOS CANC INST,DIV HEMATOL & ONCOL DETROIT MI 00000
Titolo Testata:
Environmental health perspectives
, volume: 106, anno: 1998, supplemento:, 2
pagine: 541 - 557
SICI:
0091-6765(1998)106:<541:ATSFEN>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; HUMAN-BONE-MARROW; LONG-TERM CULTURE; HUMAN IMMUNODEFICIENCY VIRUS; UMBILICAL-CORD BLOOD; C-MPL LIGAND; EOSINOPHILIA-MYALGIA-SYNDROME; DRUG-INDUCED AGRANULOCYTOSIS; CHRONICALLY IRRADIATED DOGS;
Keywords:
NEUTROPENIA; THROMBOCYTOPENIA; MYELOSUPPRESSION; MYELOTOXICITY; HEMATOTOXICITY; HEMATOTOXICOLOGY; IN VITRO ASSAY; STEM CELLS; HEMATOPOIESIS; PROGENITOR CELLS; CFU-GM; NOAEL; PERMISSIBLE EXPOSURE LIMIT; MTD; TOXICOLOGY; IND; NDA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
219
Recensione:
Indirizzi per estratti:
Citazione:
R.E. Parchment, "ALTERNATIVE TESTING SYSTEMS FOR EVALUATING NONCARCINOGENIC, HEMATOLOGIC TOXICITY", Environmental health perspectives, 106, 1998, pp. 541-557

Abstract

Hematopoietic tissues are the targets of numerous xenobiotics. Clinical hematotoxicity is either a decrease or an increase in peripheral blood cell counts in one or more cell lineages-a cytopenia or a cytosis,respectively-that carries a risk of an adverse clinical event. The purpose of in vitro hematotoxicology is the prediction of these adverse hematologic effects from the effects of the toxicants on human hematopoietic targets under controlled experimental conditions in the laboratory. Building on its important foundations in experimental hematology and the wealth of hematotoxicology data found in experimental oncology, this field of alternative toxicology has developed rapidly during the past decade. Although the colony-forming unit-granulocyte/monocyte neutrophil progenitor is most frequently evaluated, other defined progenitors and stem cells as well as cell types found in the marrow stromacan be evaluated in vitro. End points have been proposed for predicting toxicant exposure levels at the maximum tolerated dose and the no observable adverse effect level for the neutrophil lineage, and severalclinical prediction models for neutropenia have developed to the point that they are ready for prospective evaluation and validation in both preclinical species and humans. Known predictive end points are the key to successful comparisons across species or across chemical structures when in vitro dose-response curves are nonparallel. Analytical chemistry support is critical for accurate interpretation of in vitro data and for relating the in vitro pharmacodynamics to the in vivo pharmacokinetics. In contrast to acute neutropenia, anemia and acute thrombocytopenia, as well as adverse effects from chronic toxicant exposure,are much more difficult to predict from in vitro data. Pharmacologic principles critical for clinical predictions from in vitro data very likely will apply to toxicities to other proliferative tissues, such asmucositis.

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Documento generato il 26/01/20 alle ore 01:04:46