Study on cell-nuclear DNA ploidy of precancerous population for hepatocellular carcinoma and cholangiocarcinoma of humans and rats

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Analysis of cell nuclear DNA ploidy patterns of precancerous hepatocellular population derived from different induction models was done using Feulgen-reacted spectrophotometer on sliced liver tissues. Precancerous hepatocellular population including altered hepatocellular foci were obtained in two different models I1) SoltーFarber's model : single i. p. exposure of diethylnitrosamine 200 mg/kg, 2/3 hepatectomy and short term dietary exposure of N-2-fluorenylacetamide 2) continous dietary exposure of N-2-fluorenylacetamide (0.02%)]. The animals (male ACI/Nrats were sacrificed sequentially starting 4 weeks after the start of the experiment. Measurement of DNA content on the spectrophotometer (Olympus MMSP) was done using 545 nm on interphase and lymphocytes as diploid control. In the 1st and 2nd model, eosinophilic altered focus was the predominant type. DNA Ploidy pattern of this type of altered focus induced in the 1st model showed diploidization along the passage of time after the carcinogen exposure. Meanwhile, the ploidy pattern of the focus appeared in the model using continuous exposure of N-2-fluorenylacetamide did not show this tendency. The result suggests that altered hepatocelluar foci having similar phenotypic character could have different nuclear DNA ploidy pattern and the ploidy pattern of these precancerous population could depend on the induction methods including type of carcinogens and time and others. Hyperbasophilic focci infrequently appeared in both models. This type of focus had aneuploid pattern of DNA ploidy. Since many cells of hepatocellular carcinoma exhibit aneuploid pattern on DNA histogram. The results again indicate that this type of focus could be a direct precursor lesion for the hepatocellular malignancy.