title: Pathobiology of copper-induced injury in Bedlington terriers: ultrastructural and microanalytical studies.
abstract: The pathogenesis of copper (Cu)-induced liver injury has been investigated in Bedlington terriers with familial Cu toxicosis using ultrastructural and microanalytical techniques. Livers from 3 affected and 1 non-affected Bedlington terrier were fixed in 4% paraformaldehyde and 2% glutaraldehyde for transmission electron microscopy and X-ray electron probe microanalysis. Cu analysis was performed on formalin fixed liver by atomic absorption spectrophotometry. In the dog with liver Cu concentration < 2000 micrograms/g, Cu was located only in electron dense lysosomes with minimal cytoplasmic change. With increasing concentrations of liver Cu, the metal became apparent in the nucleus with early signs of nuclear disturbance. In the dog with highest liver Cu content > 7000 micrograms/g X-ray microanalysis identified Cu peaks in lysosomes, nucleus and cytoplasm in descending order with profound cellular changes. The hepatocytes were shrunken with compacted electron dense organelles and the nuclei were contracted, misshapen with chromatin condensation and fragmentation. Apoptotic bodies were identified in sinusoids. It was concluded that excess Cu is initially sequestered in lysosomes but following increasing saturation of this compartment nuclear accumulation of Cu occurs with DNA damage. Apoptosis follows probably by induction of p53 protein.
authors.affiliation: Department of Veterinary Pathology Science, University of Liverpool, UK.
authors.forename: S
authors.initials: S
authors.lastname: Haywood
authors.forename: I C
authors.initials: IC
authors.lastname: Fuentealba
authors.forename: J
authors.initials: J
authors.lastname: Foster
authors.forename: G
authors.initials: G
authors.lastname: Ross
mesh_terms: D000818:Animals; D003300:Copper / Q000009:adverse effects* / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008107:Liver Diseases / Q000235:genetics / Q000473:pathology* / Q000662:veterinary*; D009929:Organ Size / Q000187:drug effects
chemical_list: D003300:Copper