Flow cytometry of nuclear DNA content in liver cirrhosis and liver tumours in rats exposed to acetylaminofluorene

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Abstract
Male Wistar rats were fed a diet containing 0.025% of the hepatocarcinogen acetylaminofluorene (AAF). One group on animals was exposed to the carcinogen for 16 weeks, following which phenobarbitone 0.5% was added to the drinking water. Liver tumours appeared about 8 months later. Animals from this group showed no marked regenerative changes (cirrhosis or oval cell proliferation) when studied during the initial AAF-treatment. The liver tumours were well differentiated hepatocellular carcinomas and some adenomas. When analyzed by flow cytometry (FCM) these tumours were shown to contain diploid stem-lines. After a change in the housing conditions leading to a higher food intake and hence a higher dose of AAF, most of the animals in a subsequent experiment developed hepatic cirrhosis and oval cell proliferation during the initial 10 weeks of AAF-feeding. Eleven cirrhotic nodules from these animals were analyzed by FCM and showed a diploid nuclear DNA-content. Cell samples from liver tissue heavily infiltrated with oval cells also showed diploid nuclear DNA contents.