Application of fine-needle aspiration biopsy for the diagnosis of dysplastic and neoplastic liver cell changes induced by N-nitrosomorpholine in rats.

Male rats were treated with the hepatocarcinogen, N-nitrosomorpholine (NNM, 10 mg ad 100 ml drinking water) for 19 weeks. Repeated fine-needle aspiration biopsies of the liver were performed percutaneously. Cytomorphologic and cytochemical criteria were used for the characterization of dysplastic and carcinoma cells. The alterations seen in the smears were correlated with histopathologic findings in the punctured liver lobes. Cells showing type I dysplasia were recognized in smears obtained from day 7 on. They corresponded to the swollen, glycogen-free cells developing in zone 3 of the Rappaport acinus during the early treatment phases. In later stages type I dysplastic cells were observed in smears. This coincided with the development of neoplastic nodules seen in histopathologic preparations. Carcinoma cells were recognized first after 15 weeks. Marked gamma-glutamyl transpeptidase (gamma-GT) activity could be demonstrated cytochemically in biopsy smears and biochemically in biopsy homogenates during the early phases of NNM-treatment. Simultaneously, a rise in gamma-GT activity was also observed in the serum.