Carcinogen-induced abnormalities in rat liver cells and their modification by chemical agents.

Epithelial cells derived from livers of rats beamingdiethyl nitrosamine-induced hepatocancinomas were propagated in vitro and cloned. These cells exhibited acentnic nuclei and j uxtanuclear cytoplasmic lesions indistinguishable from the Mallory hyaline bodies found in the cirrhotic livers of alcoholics. The hyaline region was found to be corn pnised of a filamentous aggregate in the cytoplasm which contained components that bound concanavalin A, an in temaction that was blocked by a-methylmannopyranoside. This hepatocellular aggregate also bound immunoglobulin G from the semaof normal rabbits and from patients with advanced alcoholic cirrhosis. The immunoglobulin G frac tion of semafrom normal goats, rats, or mice did not show such an affinity. The morphological appearance of cells containing this Mallory body-like lesion was altered, in a reversible reaction, to one resembling normal rat liver epithelial cells after incubation with dimethyl sulfoxide or sodium butyrate. Such treatment also caused the cells to lose their acquired ability to localize concanavalin A and immunoglobulin G in the juxtanucleam region. The presence of the filamentous aggregate may be responsible for the acentnic displacement of the nucleus and might be come lated with the ability of the cells to express certain in vitro properties associated with the transformed state. The cyto plasmic lesion may reflect an impairment of microtubulam function and polymerization.