Biochemical Studies of Six Nitrogen-Containing Heterocycles in Rat Tissues

摘要

Female rats were orally dosed with 1/5 the LD50 of either 1-nitrosopiperidine (a carcinogen), cyclohexylamine, piperidine, 4-carboxy-1-nitrosopiperidine, 4-cyclohexyl-1-nitrosopiperidine or 2 6-dimethyl-1-nitrosopiperidine at 21 and 4 hours before sacrifice. All five noncarcinogenic compounds had no effects on any experimental parameters examined (hepatic DNA damage, ornithine decarboxylase (ODC) activity, serum alanine aminotransferase (SGPT) activity, cytochrome P-450 and glutathione content). After administration of 40 mg/kg of 1-nitrosopiperidine, significant hepatic DNA damage and a 3- to 7-fold increase in the activity of hepatic ODC were observed. 1-Nitrosopiperidine (120 mg/kg, 3/5 LD50) caused DNA damage in rat liver and esophagus but not in leukocytes. The higher dose of 1-nitrosopiperidine also decreased hepatic cytochrome P-450 content by 37% and increased hepatic ornithine decarboxylase activity by 9-fold. As ODC is often induced by tumor-promoters, 1-nitrosopiperidine may have both promoting and initiating properties. (Copyright (c) 1989 Maxwell Pergamon Macmillan plc.)