A comparative electron microscope study of early changes in rat liver induced by N-nitrosopiperidine and 2,2',6,6'-tetramethyl-N-nitrosopiperidine.

Inbred male Leeds rats were administered either the liver carcinogen N-nitrosopiperidine or the non-carcinogen 2,2',6,6'-tetramethyl-N-nitrosopiperidine in their drinking water at a concentration of 0.02%. Treatment was continued until the animals were killed, at 12 or 28 days, when their hepatic tissues were removed and examined by electron microscopy. Both compounds induced glycogen depletion, cytoplasmic fat accumulation and proliferation of the smooth endoplasmic (ER). In addition, NPIP induced mitochondrial and bile canalicular changes and marked reduction and alteration of the rough ER. The probable relationships of the observed fine structural changes to the metabolism, toxicity and carcinogenicity of these heterocyclic N-nitrosamines are discussed.