کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9029135 1561660 2005 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Benzene increases protein-bound 3-nitrotyrosine in bone marrow of B6C3F1 mice
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Benzene increases protein-bound 3-nitrotyrosine in bone marrow of B6C3F1 mice
چکیده انگلیسی
Benzene, an environmental pollutant, is myelotoxic and leukemogenic in humans. The molecular mechanisms that can account for its biological effects have not been fully elucidated. We hypothesize that one of the underlying mechanism involves nitration of proteins by peroxynitrite and/or by bone marrow myeloperoxidase-dependent pathways in nitric oxide (NO) metabolism. Using 3-nitrotyrosine [Tyr(NO2)] as a biomarker for NO-induced damage to proteins, we examined the effects of benzene on the levels of Tyr(NO2) in bone marrow in vivo. Groups of 8 weeks old B6C3F1 male mice were given a single i.p. injection of benzene (50, 100, 200 or 400 mg/kg bodyweight) in corn oil. The mice in control groups received either no treatment or a single injection of the vehicle. The mice were killed 1 h after treatment and proteins were isolated from bone marrow, lung, liver and plasma. The proteins were enzymatically hydrolyzed; amino acids were separated and purified by high pressure liquid chromatography, derivatized, and quantified by electron capture-negative chemical ionization-gas chromatography/mass spectrometry (EC-NCI-GC/MS). In the GC/MS assay, 3-nitro-l-[13C9]tyrosine was used as an internal standard and l-[2H4]tyrosine served to monitor artifactual formation of 3-nitrotyrosine during sample preparation and analysis. We found that treatment of mice with benzene elevates nitration of tyrosine residues in bone marrow proteins. There was a dose (50-200 mg benzene/kg b.w.)-dependent increase in protein-bound Tyr(NO2) formation (1.5- to 4.5-fold); however, the levels of Tyr(NO2) at 400 mg benzene/kg b.w. were significantly higher than control but lower than that formed at 200 mg benzene/kg b.w. The results of this study, for the first time, indicate that benzene increases protein-bound 3-Tyr(NO2) in bone marrow in vivo, and support our previous finding that benzene is metabolized to nitrated products in bone marrow of mice; collectively, these results may in part account for benzene-induced myelotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 156, Issues 2–3, 20 October 2005, Pages 81-91
نویسندگان
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