دورية أكاديمية

Cellspecific activation and detoxification of benzene metabolites in mouse and human bone marrow: identification of target cells and a potential role for modulation of apoptosis in benzene toxicity

التفاصيل البيبلوغرافية
العنوان: Cellspecific activation and detoxification of benzene metabolites in mouse and human bone marrow: identification of target cells and a potential role for modulation of apoptosis in benzene toxicity
المؤلفون: David Ross, David Siegel, Diane G. Schattenberg, Xiaoming M. Sun, Julie L. Moran
المساهمون: The Pennsylvania State University CiteSeerX Archives
المصدر: ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/e2/a7/Environ_Health_Perspect_1996_Dec_104(Suppl_6)_1177-1182.tar.gz
سنة النشر: 1996
المجموعة: CiteSeerX
مصطلحات موضوعية: Key words, benzene, cell-specific metabolism, myeloperoxidase, NAD(P)H, quinone oxidoreductase, phenol, catechol, hydroquinone, apoptosis, stromal cells, CD34+ cells
الوصف: The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimide adenine dinucleotide phosphate, reduced [NAD(P)Hl:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34+ progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting
نوع الوثيقة: text
وصف الملف: application/zip
اللغة: English
العلاقة: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.277.2911Test
حقوق: Metadata may be used without restrictions as long as the oai identifier remains attached to it.
رقم الانضمام: edsbas.FE07137E
قاعدة البيانات: BASE