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© 1992 Oxford University Press

research-article

Sequential Study in Rats of Nasal and Hepatic Lesions Induced by N-Nitrosodimethylamine and N-Nitrosopyrrolidine

C. RANGGA-TABBU and S. D. SLEIGHT3

Department of Pathology, Michigan State University East Lansing, Michigan 48824

Received September 9, 1991; accepted January 21, 1992

Female Sprague-Dawley rats were given an ip dose of N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR), singly or in combination, and the sequential development of lesions in the liver and nasal cavity was characterized. Liver and nasal tissues were collected from rats given either NDMA or NPYR and killed at 6 or 12 hr and 1, 3, 10, or 30 days. After combination exposure, rats were killed at 3 or 30 days. Olfactory epithelium and adjacent Bowman's glands were specifically targeted by each chemical. Lesions were seen as early as 6 hr and were most severe by 3 days. At the high doses (60 mg/kg NDMA or 100 mg/kg NPYR) regeneration was not complete by 30 days. Hepatic necrosis was seen at 1 and 3 days with NDMA but was not seen with NPYR. Combination exposure appeared to cause additive effects in both the liver and the nasal cavity. Results indicate that a single ip administration of NDMA or NPYR can induce severe and prolonged toxic effects on nasal tissues in rats.


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