Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Hepatology (Baltimore); (USA)

DOI:https://doi.org/10.1002/hep.1840120622· OSTI ID:6150479

Smith, A G; Carthew, P; Francis, J E; Edwards, R E; Dinsdale, D ^[1]

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1. MRC Toxicology Unit, Carshalton, Surrey (England)

After a single subcutaneous dose of iron-dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67-, 42- and 21-fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron-positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of the study, the size of the inclusions (which were not membrane-limited) increased to greater than 3 microns in diameter, occupying greater than 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x-ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope. These findings are consistent with the hypothesis that in iron-loaded mouse hepatocytes there is a slow passage of ferritin-molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes.

• OSTI ID: 6150479
• Journal Information: Hepatology (Baltimore); (USA), Vol. 12:6; ISSN 0270-9139
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
FERRITIN
BIOLOGICAL ACCUMULATION
IRON
METABOLISM
CELL NUCLEI
CHEMICAL COMPOSITION
CYTOPLASM
ELECTRON MICROPROBE ANALYSIS
HYDROXYL RADICALS
LIVER
LYSOSOMES
MACROPHAGES
MICE
PHOSPHORUS ISOTOPES
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BODY
CELL CONSTITUENTS
CHEMICAL ANALYSIS
COMPLEXES
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
ELEMENTS
GLANDS
IRON COMPLEXES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METALLOPROTEINS
METALS
MICROANALYSIS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PHAGOCYTES
PROTEINS
RADICALS
RODENTS
SOMATIC CELLS
TRANSITION ELEMENT COMPLEXES
TRANSITION ELEMENTS
VERTEBRATES
550501* - Metabolism- Tracer Techniques