Subcellular Distribution of Curium in Beagle Liver

The subcellular distribution of curium (<tex-math>${}^{243,244}{\rm Cm}$</tex-math>) was studied in canine liver from 2 hr to 47 days after injection of <tex-math>$3\ \mu {\rm Ci}^{243,244}$</tex-math> Cm/kg of body weight. The pattern of distribution for Cm was similar to other trivalent actinide elements studied previously (Am, Cf). Initially (2 hr), most of the nuclide was found in the cytosol and at least 90% was protein bound. About 70% of the Cm was bound to ferritin, ∼5% was associated with a protein of MW ∼200,000, and ∼25% was found in the low-molecular-weight region (∼5000). The decrease in the Cm content of cytosol, nuclei, and microsomes coincided with an increase in the amount associated with mitochondria and lysosomes. The concentration of the Cm in the mitochondrial fraction was higher than it was in the lysosomal fraction at each time studied. In the mitochondrial fraction ∼30% of the Cm was bound to membraneous or granular material, and 70% was found in the soluble fraction. The Cm concentration initially associated with cell nuclei was high but had diminished to 20% of the 2 hr concentration by 20 days post injection (PI). The subcelluar distribution of Cm in the liver of a dog which had received the same dose and was terminated because of severe liver damage was studied at 384 days PI. The liver weighed 130 g and contained approximately 30% of the injected Cm. In contrast, a normal liver weighs 280 g and at 2 hr PI contains approximately 40% of the injected dose. The subcellular distribution of Cm in this severely damaged liver differed from the pattern observed at earlier times after injection. The relative concentration of Cm in the cytosol was doubled, it was higher in the nuclei-debris fraction; and it was lower in the mitochondrial and lysosomal fractions when compared to earlier times.