Cellular basis of induced α-fetoprotein synthesis by hepatocytes of adult mouse after hepatotoxic injury and partial hepatectomy

Abstract

The dynamics of α-fetoprotein (AFP) production by hepatocytes following different experimental manoeuvres that are known to induce regeneration of the liver was studied in young adult mice by simultaneous identification of dividing cells arrested during mitosis and of cells containing immuno-histochemically detectable AFP. After 70% hepatectomy AFP was produced by a few, largely periportally located hepatocytes, following waves of brisk and active cell division. Carbon tetrachloride (CCl₄)-induced hepatic injury, on the other hand, led to participation of a relatively larger number of cells in early AFP synthesis preceding a less extensive cell proliferation. Initially, AFP-producing cells were located in the peripheral part of the lobule but later they were more centrally placed, most often surrounding the zone of necrosis. Cells in mitosis often contained large amounts of AFP. CCl₄ administration 48 h after 70% hepatectomy resulted in extensive AFP production by approximately a quarter of all surviving liver cells, although the concurrent rate of cell division was low. Intoxication with dimethylnitrosamine showed a pattern identical to that of hepatectomy but both cell division and AFP production were of comparatively lower magnitude. It is concluded that at least two distinct modes exist for augmented synthesis of AFP by hepatocytes of adult animals. In one, pre-existent cells are stimulated to produce the protein before and irrespective of cell division while in the other, small amounts are synthesized by newly generated cells. Combination of the two mechanisms results in high levels of AFP production by stimulation of a large number of young hepatocytes.