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Cytological Aspects of Normal and Tumorous Liver^*

( Cell Research Laboratory, The Mount Sinai Hospital, New York, New York; and Department of Physiology, Ohio State University, Columbus, Ohio)

Liver tumors were induced in male rats of the Wistar strain by feeding p-dimethylaminoazobenzene mixed into ground rat food. Surgical biopsies were taken before the animals were fed the azo dye, after 18 weeks of feeding, and when the animals were sacrificed. Tumorous liver was classified as cholangioma, trabecula hepatoma, and apparently normal areas. DNA content (by cytophotometry), mitotic activity, and nuclear volumes were obtained for the normal liver and different areas of the tumorous liver and were compared with earlier biopsies in each individual animal.

Normal parenchymal cells contained three DNA classes; the third class increased in frequency with age. Nuclear volumes were closely grouped around each DNA class. Enlarged nuclei belonging to DNA classes higher than the third class appeared after 18 weeks of feeding the azo dye. Mitotic indices in these tissue samples were within the normal range.

Apparently normal areas in the tumorous liver contained enlarged nuclei belonging to DNA classes higher than the third class, and again the mitotic index was not increased. A high mitotic index was observed in proliferating trabecula hepatoma areas, and consistent with this were many DNA values lying between the DNA classes. DNA measurements made with the two-wavelength method on interphase nuclei and on chromosome groups in dividing cells again revealed intermediate values. Intermediate values from interphase nuclei were thought to be due to either DNA synthesis or chromosome aberrations; however, intermediate values from chromosome groups were probably due to some type of chromosome aberration.

Normal bile duct cells contained a single DNA class, the diploid. Nuclear volumes were closely grouped around this class. Cholangioma nuclei were greatly enlarged but were still associated with a single diploid DNA class. The mitotic index in cholangioma was about the same as that in normal bile duct cells.

^* This work was done at Ohio State University under tenure of a predoctoral fellowship, N.I.H.

Received 5/24/62.