Phenobarbital-induced cytoplasmic accumulation of β1-integrin in rat liver enzyme altered foci; an immunohistological study

In this immunohistological study we investigated integrin expression in EAF in female rats treated with diethylnitrosamine (DEN) as initiator and phenobarbital (PB) as promotor (DEN-PB treatment) for up to 32 weeks. Using a β1-integrin antibody, there was an increased cytoplasmic staining and a decreased sinusoidal staining in EAF, as compared to non-EAF areas. The majority of small EAF and all larger EAF exhibited this altered distribution of β1-integrin. The increased cytoplasmic staining was not found in EAF after a 10 week treatment-free period. In periportal areas in partial hepatectomized control rats a similar increase in cytoplasmic staining was seen. EAF in DEN-initiated and DEN-promoted rats (DEN-DEN treatment) were also studied. This protocol induced rapidly growing EAF. Most lesions did not show the increased cytoplasmic staining. However, after partial hepatectomy of DEN-DEN-treated rats, a cytoplasmic staining was seen in EAF. It is concluded that PB induced a reversible cytoplasmic β1-integrin expression in many EAF and in all larger EAF. It is suggested that the alteration constitutes part of hepatocyte resistance to toxicological stress and apoptosis in EAF.