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S Thorgeirsson

Publications and source records attributed to S Thorgeirsson.

8 recordsLinked to original sources
PubMed1997

Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells.

BACKGROUND/AIMS: Biliary epithelial cells (ductular oval cells) migrate into the periportal and midzonal parenchyma when hepatocyte regeneration after injury is significantly impeded. The potential of oval cells to differentiate into hepatocytes has been questioned. We have sought to resolve this issue using the modified Solt-Farber procedure in which 2-acetylaminofluorene is used to block hepatocyte regeneration in partially hepatectomized rats. METHODS: Rats received 2-acetylaminofluorene by oral gavage for 6 days before and up to 7 days after a two-thirds hepatectomy. The cellular reaction was visualized by the immunohistochemical localization of intermediate filaments cytokeratins 8 and 19 and vimentin, cytochrome P450 enzymatic proteins and alpha-foetoprotein. Expression of albumin and alpha-foetoprotein mRNA transcripts were observed in situ using antisense riboprobes. RESULTS: During the first 9 days after partial hepatectomy long strings of ductular cells spread outwards from the portal areas. These cells exhibited strong diffuse cytoplasmic staining with the anticytokeratin 8 and 19 antibodies, like authentic bile ducts, but in addition also expressed vimentin and alpha-foetoprotein (protein and mRNA)-collectively termed the "oval cell phenotype". Thereafter, these ducts rapidly vanished to be replaced by basophilic hepatocytes which lacked the oval cell phenotype, but which acquired strong expression of albumin mRNA. At 14 days after partial hepatectomy the oval cell phenotype was restricted to the peripheral margins of the newborn periportal hepatocytes, the distal tips of the oval cell ducts, and these too had disappeared within another 7 days. CONCLUSIONS: Ductular oval cells will differentiate into hepatocytes under appropriate experimental conditions.

Albumins↗
PubMed1996

Induction of hepatic aneuploidy in vivo by tamoxifen, toremifene and idoxifene in female Sprague-Dawley rats.

Since tamoxifen is efficacious for the prevention of second primary breast neoplasms in humans and has a low reported incidence of acute side effects, several structurally related compounds have been developed for the treatment of breast cancer including toremifene and idoxifene. We have compared the karyotypic alterations that occur after a single per os administration of 35 mg/kg of tamoxifen, toremifene or idoxifene to female Sprague-Dawley rats. One day following treatment, the rats were sacrificed and the hepatocytes isolated and cultured. After 47 h in culture, colcemid was added for 3 h prior to harvest of the hepatocytes for karyotypic evaluation. At least 100 metaphase spreads were examined for each of five rats per treatment. Toremifene resulted in aneuploidy in 50 +/- 7% of the cells examined and idoxifene induced a 57 +/- 4% aneuploidy compared with the 85 +/- 7% level induced by tamoxifen. Since the level of aneuploidy in solvent-treated rats was 3 +/- 3 %, the induction of aneuploidy in at least 50% of the cells from rats treated with tamoxifen, toremifene or idoxifene was highly significant. Analysis of electron micrographs of cultures treated with these antiestrogens demonstrated a range of phenotypes including multipolar spindles in toremifene-treated rats and condensed chromosomes in the presence of an intact nuclear envelope in occasional idoxifene-treated rat hepatocytes. The exclusion of chromosomes from the spindle apparatus and the lagging of some chromosomes on the metaphase plate correlate with the high rate of induction of aneuploidy in the rat liver as determined by karyotypic analysis of hepatocytes from rats treated with these triphenylethylenes.

Aneuploidy↗
PubMed1986

Induction of peroxisome proliferation in hepatocytes transplanted into the anterior chamber of the eye. A model system for the evaluation of xenobiotic-induced effects.

The effect of two hypolipidemic peroxisome proliferators, ciprofibrate and di(2-ethylhexyl)phthalate (DEHP), on hepatocytes transplanted into the anterior chamber of the eye was examined. Young male F-344 rats transplanted with dissociated hepatocytes were fed either a control diet or a diet containing 0.025% ciprofibrate or 2% DEHP. After 4-5 weeks of treatment, all rats were sacrificed and the transplanted liver cells and portions of homotopic liver were processed for light and electron microscopy and for immunofluorescence microscopy. Morphometric analysis of transplanted hepatocytes showed a ninefold and fivefold increase in the volume density of peroxisomes in ciprofibrate and DEHP-fed rats, respectively. Indirect immunofluorescence studies revealed a marked induction of peroxisome-associated enzymes. From these data it is concluded that hepatic peroxisome proliferators cross the blood aqueous humor barrier and the transplanted hepatocytes in the anterior chamber of the eye retain their ability to recognize and respond to peroxisome proliferators.

Animals↗