کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2595398 1562304 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metabolism and excretion of 1-hydroxymethylpyrene, the proximate metabolite of the carcinogen 1-methylpyrene, in rats
ترجمه فارسی عنوان
متابولیسم و دفع 1-hydroxymethylpyrene، متابولیت تقریبی از 1-methylpyrene سرطان زا در موش
کلمات کلیدی
1-Methylpyrene؛ 1-Hydroxymethylpyrene؛ متابولیسم موش صحرایی؛ هیدروکربن های آروماتیک چندحلقه‌ای alkylated
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی

1-Methylpyrene, an alkylated polycyclic aromatic hydrocarbon and environmental carcinogen, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1-HMP) and subsequent sulfo conjugation to the DNA-reactive 1-sulfooxymethylpyrene. In addition to the bioactivation, processes of metabolic detoxification and transport greatly influence the genotoxicity of 1-methylpyrene. For a better understanding of 1-HMP detoxification in vivo we studied urinary and fecal metabolites in rats following intraperitoneal doses of 19.3 mg 1-HMP/kg body weight (5 rats) or the same dose containing 200 μCi [14C]1-HMP/kg body weight (2 rats). After 48 h, 48.0% (rat 1) and 29.1% (rat 2) of the radioactivity was recovered as 1-HMP in the feces. Six major metabolites were observed by UV and on-line radioactivity detection in urine samples and feces after HPLC separation. The compounds were characterized by mass spectrometry, 1H NMR and 1H-1H COSY NMR spectroscopy, which allowed assigning tentative molecular structures. Two prominent metabolites, 1-pyrene carboxylic acid (M-6) and the acyl glucuronide of 1-pyrene carboxylic acid (M-5) accounted for 17.7% (rat 1) and 25.2% (rat 2) of the overall radioactive dose. Further, we detected the acyl glucuronide of 6-hydroxy-1-pyrene carboxylic acid (M-1) and 8-sulfooxy-1-pyrene carboxylic acid (M-3) together with two regioisomers of M-3 (M-2 and M-4) differing in position of the sulfate group at the pyrene ring. In urine samples, the radioactivity of 1-pyrene carboxylic acid and its five derivatives amounted to 32.4% (rat 1) or 45.5% (rat 2) of the total [14C]1-HMP dose.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volumes 366–367, 29 July 2016, Pages 43–52
نویسندگان
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