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Distribution of N-Nitrosomethylbenzylamine Evaluated by Whole-Body Radioautography and Densitometry¹

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

The distribution of N-nitrosomethylbenzylamine (MBN) was studied using whole-body radioautography and densitometry. Male Sprague-Dawley rats were given N-nitroso-[methyl-¹⁴C]-benzylamine ([methyl-¹⁴C]MBN) (3.3 mg, 1 mCi/kg body weight i.p.) or N-nitrosomethyl[benzyl-7-¹⁴C]amine (2.1 mg, 1 mCi/kg body weight i.p.), and sagittal sections were taken at 15 min, 60 min, 3.5 hr, 7.25 hr, 24 hr, and 3 days after injection.

Very high levels of [methyl-¹⁴C]MBN-derived radioactivity were present at all time periods (15 min to 3 days) in the three target tissues for MBN-induced tumorigenesis (nasal cavity, lung, and esophagus). The liver contained high and the kidney contained moderately high levels of radioactivity at all time periods. A considerable amount of radiolabel was present in a number of tissues at 24 hr. After 3 days, very high levels were observed only in the tissues in which MBN-induced tumors eventually developed.

Following administration of N-nitrosomethyl[benzyl-7-¹⁴C]amine, levels of radioactivity in most tissues were lower than following injection of [methyl-¹⁴C]MBN; however, very high levels were present in the nasal cavity, liver, and kidney. Considerably less radiolabel remained at 24 hr and 3 days following injection of N-nitrosomethyl[benzyl-7-¹⁴C]amine than following [methyl-¹⁴C]MBN administration. At 24 hr, benzyl moiety-derived radiolabel was present in either the enterohepatic circulation or the tissues in which MBN-induced tumors arose. At 3 days, the highest level of radioactivity was contained by the liver, although detectable levels remained in the nasal cavity and lung, two tissues in which MBN induced carcinomas.

The findings of this study indicate that the carcinogenicity of MBN may be the result of the inability of the target organs (esophagus, nasal cavity, and lungs) to readily clear methylated macromolecules, benzylated macromolecules, or the oxidized metabolites which arise during nitrosamine metabolism.

¹ This work was supported in part by Research Grant 2-PO1-ES00597 from the National Institute of Environmental Health Sciences, NIH.

² Recipient of a National Research Service Award 1-T32-ES-07020 from the National Institute of Environmental Health Sciences, NIH.

³ To whom requests for reprints should be addressed.

Received 8/31/79. Accepted 2/28/80.

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