Albumin Metabolism in Rabbits and Rats with Transplanted Tumours

Abstract

SUMMARY.-Albumin distributions and turnover rates have been studied using 131I labelled tracer material in rabbits with Vx2 carcinoma and rats bearing SP7 fibrosarcoma in comparison with control animals. Albumin concentrations were reduced in the tumour bearing animals but plasma volumes increased as the tumours developed. Relative increases were seen in the extravascular distribution of albumin, due partly to albumin pooling in and around the tumours and possibly also to general increases in capillary permeability. In the rats there was a considerable increase in the catabolic rate of albumin which was not related to urinary protein loss. The tumour bearing rabbits showed evidence both of increased catabolism and of decreased synthesis and the combination of the two effects resulted in a greater lowering of albumin concentration than was seen in the rats. Possible mechanisms for these findings and their significance in human malignant disease are discussed.A NUMBER of albumin turnover studies have been earried out in cancer patients (Steinfeld, 1960;Waldman et al., 1963; Wetterfors etal., 1962; Jarnum and Schwartz, 1960;Cohn et al., 1966;Sum et al., 1964) to try to elucidate the causes of the hypoalbuminaemia which often accompanies malignant disease (Mider et al., 1950). External protein leakage, decreased synthesis, increased catabolism and additional extravascular albumin pools have all been reported. The impossibility of obtaining a well-defined homogeneous group of subjects with malignant disease and the difficulty of defining a valid grodp of controls for comparative measurements probably contribute to discrepancies between the various reports.Studies in tumour bearing animals can avoid these particular problems. Norberg and Greenberg (1951), using mice, and Hradec (1958), using rats, studied the rate of uptake of labelled amino-acids by plasma proteins in tumour bearing animals. Babson (1956) and Hradec (1958) measuredthe slope oftheintravascular retention curve after injecting labelled albumin into rats with Walker carcinomas. All these studies suggested that plasma protein turnover rates are increased by the presence oftumours. However, the interpretation ofthe uptake studies is uncertain because of differences in competition for amino-acids from other tissues. The other studies did not examine the turnover kinetics in any detail nor did they differentiate between loss of tracer from the circulation by equilibration with extravascular albumin, and loss by catabolism. In addition Dinh and Brassard (1968) have shown greatly increased renal protein losses in rats with Walker carcinomas.The present work was carried out to investigate the turnover and the distribution of albumin in rabbits implanted with Vx2 carcinoma (experiments A and B) and in rats bearing SP7 fibrosarcoma (experiment C).

Capillary permeability to protein as a factor in the control of plasma volume

“…Rusznyak (1924) pointed out that a reduction in plasma colloid osmotic pressure does not necessarily lead to a reduction in plasma volume as would be expected (Rusznyak, Foldi & Szabo, 1967). In a number of pathological conditions such as cirrhosis (Lieberman & Reynolds, 1967), nephrotic syndrome (Jensen, Rossing, Andersen & Jarnum, 1967) and malignant disease (Wraight, 1971), the plasma volume is often maintained or even increased in spite of reductions in colloid osmotic pressure. The same situation occurs following plasmapheresis in dogs (Burgen & Francombe, 1962;Rusznyak et al 1967), rabbits (Matthews, 1961) and man (deduced from figures given by Andersen & Rossing, 1967).…”