Phenobarbital-induced cytoplasmic accumulation of beta1-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 beta1-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 beta1-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 beta1-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.
Stenius
U
U
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Högberg
J
J
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004052:Diethylnitrosamine / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D019012:Integrin beta1; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D001973:Bromodeoxyuridine; D010634:Phenobarbital