ARRAY OF MITOCHONDRIAL ALTERATIONS IN THE HEPATOCYTES OF LONG-EVANS CINNAMON RATS

Zn an attempt to identify the cellular targets of copper toxicity, we studied the ultrastructure of hepatocytes in the livers of 23 Long-Eva ns Cinnamon (LEG) rats ranging in age from 10 to 89 weeks, The hepatic copper concentration ranged from 325 to 2,126 (mean, 930) mu g/g dry weight. Thirteen rats displayed varying degrees of jaundice at the tim e of killing, Numerous nuclei were indented by cytoplasmic invaginatio ns, Conspicuous abnormalities were displayed by mitochondria. These in cluded marked pleomorphism; increased or diminished matrical density; rearrangement, elongation, dilatation, stacking, or disappearance of c ristae; absence of matrical granules; presence of matrical inclusions of flocculent electron-dense deposits; and degenerative changes, The s everity of the ultrastructural changes did not correlate with the hepa tic copper concentration but did correlate with the degree of the icte rus displayed by the rats, Certain mitochondrial changes resembled tho se encountered in the hepatocytes of patients with Wilson's disease, c onfirming that these organelles are important targets of copper toxici ty.