کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9028610 1561662 2005 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Topoisomerase II inhibition by myeloperoxidase-activated hydroquinone: A potential mechanism underlying the genotoxic and carcinogenic effects of benzene
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Topoisomerase II inhibition by myeloperoxidase-activated hydroquinone: A potential mechanism underlying the genotoxic and carcinogenic effects of benzene
چکیده انگلیسی
Benzene is an established human and animal carcinogen. While many of the key mechanisms underlying its carcinogenic effects remain unknown, there is increasing evidence that chromosomal alterations play an important role in the development of the induced leukemias. Inhibition of enzymes involved in DNA replication and maintenance such as topoisomerases by benzene metabolites represents a potential mechanism by which benzene may induce its chromosome-altering effects. Previous work from our laboratory and others has demonstrated that bioactivated benzene metabolites are capable of inhibiting topoisomerase II (topo II) in isolated enzyme and cell systems as well as in mice administered benzene in vivo. The current studies were designed to build upon this hypothesis, and show that in the presence of human myeloperoxidase and H2O2, hydroquinone can be activated to a potent topo II inhibitor. In the absence of dithiothreitol, partial inhibition can be seen at hydroquinone concentrations as low as 50 nM. The potential role of topo II inhibition in the development of benzene-induced leukemia is also discussed in the context of other known leukemia-inducing agents. Current evidence indicates that multiple mechanisms are likely to contribute to benzene-induced leukemias, and that inhibition of topo II could represent an important step in the development of certain leukemia subtypes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volumes 153–154, 30 May 2005, Pages 207-216
نویسندگان
, , ,