Time-course of iron overload and biochemical, histopathological and ultrastructural evidence of pancreatic damage in hypotransferrinaemic mice.
1. The time course of iron overload of the pancreas in hypotransferrinaemic mice maintained on a standard rodent diet was compared with biochemical and histological markers of tissue damage. 2. Pancreatic iron levels increased linearly from weaning till 9 months of age [73.3 nmol/mg of tissue (SEM 9.9; n = 5) compared with 0.9 nmol/mg of tissue (SEM 0.1; n = 4) in age-matched controls] then decreased linearly till at least 18 months of age. 3. Investigation of tissue distribution of newly absorbed radioiron suggested that significant redistribution of iron from liver to pancreas (rather than direct dietary iron sources) must be invoked to explain the rate of pancreatic iron loading in hypotransferrinaemic mice. 4. Pancreatic epithelial cells first showed altered morphology at 9 months of age. At 12 months of age, the pancreatic epithelium had developed a micronodular appearance, with large numbers of acini replaced by atrophic, degenerated acinar cells. Increased collagen fibre deposition was evident by trichrome staining and by electron microscopy. Biochemical markers of pancreatitis (serum lipase, tissue pancreatitis-associated protein mRNA) were elevated before 9 months of age, whereas the levels of pancreatic amylase mRNA declined from 9 months of age. 5. The data suggest that iron loading of hypotransferrinaemic mouse pancreas proceeds up to a threshold level at 9 months of age followed by a progressive atrophy of secretory epithelium. The hypotransferrinaemic mouse pancreas is a useful model system for investigation of parenchymal cell damage by iron.
Simpson
R J
RJ
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, U.K.
Deenmamode
J
J
McKie
A T
AT
Raja
K B
KB
Salisbury
J R
JR
Iancu
T C
TC
Peters
T J
TJ
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000681:Amylases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000951:Antigens, Neoplasm; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type; D008049:Lipase / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008954:Models, Biological; D010179:Pancreas / Q000378:metabolism* / Q000648:ultrastructure; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014168:Transferrin / Q000172:deficiency*
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C490253:Reg3b protein, mouse; D014168:Transferrin; D008049:Lipase; D000681:Amylases