Distributionof N-NitrosomethylbenzylamineEvaluatedby Whole-Body Radioautographyand Densitometry1
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چکیده
derivatives of MBN display striking differences in mutagenicity (19). Of interest because of its structure, toxicity, organ-spe cific carcinogenicity, and mutagenicity of oxidized derivatives, we undertook an extensive investigation of MBN which encom passed toxicity and carcinogenicity testing, pharmacokinetic and metabolic studies, and tissue distribution and persistence evaluations. The latter topic is the focus of the present report. Whole-body radioautography was performed at 6 time points after injection of [14CJMBN.The 4 earlier time points were chosen to reflect tissue distribution and uptake. Tissue per sistence of radiolabel was determined at the 2 later time pe nods. Densitometric analysis of the radioautograms permitted the calculation of half-lives of dpm equivalents in selected tissues. Whole-body radioautography has recently been used to investigate the distribution of DMN and MBN (9, 10). In the latter study, a dose of N-methyl[U-3H]-N-nitrosobenzylamine producing acute toxicity (100 mg, 10 mCi/kg body weight i.v.) was administered to male Donryu rats. In the present study, a fraction of the 50% lethal dose of MBN was administered to male Sprague-Dawley rats, and the use of [14C]MBN circum vented the problem of loss of tritium due to hydrogen exchange and metabolism of the nitrosamine.
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تاریخ انتشار 2006