Altered capacities for amino acid transport in response to liver injury by CC14 and during subsequent regeneration

Abstract

Exposure of rats to CCl₄ resulted in necrosis of the acinar zone 3 associated with the disappearance of glutamine synthetase-positive pericentral hepatocytes. Histologic and immunohistochemical observations indicated the almost complete remodelling of the pericentral zone within 2 weeks. Immediately after intoxication as well as during subsequent regeneration dramatic changes in the extent of the hormonal regulation of the amino acid transport systems A, N, and G^– were noted in cultured hepatocytes characterized by the individual response of each system. The changes occurring during the regenerative period could partially be mimicked by inducing transient hepatocyte proliferation through plating at low cell density and addition of growth factors in vitro. It is obvious from these results that the alterations in the induction of hepatic amino acid transport systems observed after CCl₄ intoxication are due to: (a) disturbance and reacquisition of acinar heterogeneity, (b) onset and finish of hepatocellular proliferation.