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Utilization of Electron Probe Microanalysis in Gadolinium-Treated Mice

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000

Thomas M. Monticello

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000

Robert S. Feldman

Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903-0191

Peter H. Gitlitz

Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903-0191

Stephen K. Durham

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000

Gadolinium is used as a contrast media for magnetic resonance imaging and, experimentally, to block Kupffer cell phagocytosis. In this study, we utilize electron probe microanalysis to determine the subcellular localization of gadolinium chloride (GdCl ₃) administered to mice in a short-term toxicology study. Male CD-1 mice were administered 0.0, 2.5, or 8.0 mg/kg GdCl₃ iv for 14 consecutive weekdays. Liver-associated enzymes were significantly elevated in high-dose animals only and correlated histologically with multifocal, hepatocellular degeneration associated with a neutrophilic infiltrate. Morphological investigations were performed on high-dose animals. Hepatocytes and Kupffer cells had morphologic features of cellular injury consisting of swollen mitochondria and vesiculated profiles of endoplasmic reticulum. Hepatocytes, Kupffer cells, bile canaliculi, and neutrophils in the liver contained discrete aggregates of electron-dense granular material, as did pulmonary interstitial macrophages, splenic macrophages, and mesangial cells of the renal glomerulus. The intracellular granular material in the liver, lung, spleen, and kidney was confirmed as gadolinium by qualitative electron probe microanalysis. These results document both hepatic and extra-hepatic accumulation of gadolinium in cells of the mononuclear phagocytic system and highlight the importance of electron probe microanalysis in toxicologic assessment.

Key Words: Liver • mononuclear phagocytic system • toxicology • electron microscopy

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Toxicologic Pathology, Vol. 24, No. 5, 588-594 (1996)
DOI: 10.1177/019262339602400508


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