The Binding of Americium and Plutonium to Bone Glycoproteins

Abstract

By means of a gel filtration technique it is shown that plutonium and americium differ in their mode of binding to two glycoproteins isolated from bovine cortical bone. Plutonium binds more strongly than americium, plutonium binding is maximal a t pH 6 and americium a t p H 8, and sialic acid is involved in the binding of plutonium but not americium. The mechanisms by which these elements bind to glycoproteins in vitro are discussed.A number of metals are now known to concentrate in bone where they may cause serious pathological disturbances, including neoplasia. Some metals, for example strontium and radium, are associated with the hydroxyapatite of the mineral phase, but others, such as yttrium or the radioelements of the transuranic group, deposit predominantly in resting and resorbing areas on the endosteal and, to a lesser extent, periosteal surfaces of bone [I]. More information of the mechanisms of deposition of metals in bone would help to increase our understanding of both the general biochemistry of bone and of the induction of bone cancer and other pathological conditions by radioactive or non-radioactive metals deposited in bone.Observations of the deposition of yttrium, plutonium and americium in bone suggested that these elements might be bound by mucosubstances present at the bone surfaces [2,3]. The glycoproteins of bovine cortical bone have been studied extensively by Herring [a] and the binding of heavy metals to some of these substances has been demonstrated by other workers [5,6].So far two glycoprotein components of bovine bone have been described in detail [7]. The first is bone sialoprotein, a glycoprotein of molecular weight 25000 f 500 containing 40°/,, by weight of carbohydrate [8,9]: it is unusual in its high content of sialic, aspartic and glutamic acids [9]. The second is the bone chondroitin sulphate-protein complex [ 101 or, more correctly, the three chondroitin sulphateprotein complexes. The compositions of these three complexes are consistent with their being either free chondroitin sulphate or one or two chondroitin sulphate chains attached to a protein core whose properties appear t o be similar to those of bone sialoprotein [lo]. There are also other glycoproteins in bovine cortical bone The study of the binding of heavy metals to proteins is complicated by the pronounced tendency of such metals to hydrolyse a t neutral pH. Consequently it is not easy to use conventional methods for the study of reactions between proteins and heavy metals. This report describes the application of a previously published gel filtration procedure [ll] to the study of the mechanisms of binding of americium to bone sialoprotein and of plutonium and americium to the chondroitin sulphate-protein complex of bovine cortical bone. MATERIALS AND METHODS MaterialsBone sialoprotein and the chondroitin sulphateprotein complex, i.e. the mixture of the three complexes as normally prepared, were isolated from bovine cortical bone by methods based on those of Herring [4]. The later stages of these preparati...

Interpretation of Enhanced Fecal and Urinary Plutonium Excretion Data under a 2-y Regular DTPA Treatment Started Months after Intake

“…1 and Table 1). Even though plutonium deposits established in bone tissue are usually considered to be retained tenaciously (Chipperfield and Taylor 1970, 1972) and hence not easily removable by DTPA (Guilmette et al 2003) in humans, James et al observed an ability of multiple DTPA treatments to reduce skeletal plutonium level, predominantly from trabecular bone surfaces (James et al 2007). With regard to the liver, a chelation of hepatic transuranic deposits in animals (Bhattacharyya et al 1978; Grémy et al 2016) and humans (Roedler et al 1989; James et al 2007) has been reported by several authors.…”

The distribution and retention of plutonium, americium and uranium in CBA/H mice

“…It has been suggested that the binding molecules are glycoproteins or proteoglycans, constituents of the osteoid layer of unmineralised new bone on growing surfaces. [43][44][45][46] However, this suggestion is not consistent with the presence of 239Pu and 241 Am on all types of bone surface, including resting and resorbing areas, and the observation that 239PU on growing surfaces is largely concentrated on the surface of the mineralised bone .47 Other studies have implicated phosphoproteins, demonstrating the ability of molecules in mineralising rat dentine to bind lanthanum; 48 binding to phospholipids has also been suggested. 49 Recently, uptake of radium from transferrin and incorporation into ferritin in osteoblasts has been demonstrated.5° Uptake into osteoblasts may also occur for 239Pu and 241 Am with important implications for their potential to induce osteosarcoma.…”