Regression of Transplanted Lymphomas Induced in Vivo by Means of Normal Guinea Pig Serum

Abstract

In an extension of the experimental studies recorded in an associated paper; attempts were made to isolate and characterize the constituent of guinea pig serum responsible for inducing regression of transplanted lymphomas in vivo. The active material was precipitated readily from the whole serum, along with some of the globulins, by means of ammonium sulfate in concentrations of 2.0 molar or greater; it withstood heating at 56°C. for 20 or 30 minutes, but was inactivated upon heating at 66°C. for similar periods; it was completely inactivated by chymotrypsin in concentrations of 1 or 2 mg./cc. during 6 hours at 37°C. Furthermore, the inhibitory effects of small amounts of the guinea pig serum in vivo were enhanced upon admixture with immune sera prepared by injecting the lymphosarcoma cells into rabbits. The facts as a whole suggest that the active material is a protein, and that it may be one or another of the components of complement; yet they do not suffice to establish its identity. Microscopic studies showed that the cells of subcutaneous lymphomas rapidly died and were resorbed following injections of relatively large amounts of guinea pig serum intraperitoneally into mice carrying them, while similar changes followed more gradually after repeated injections of smaller amounts of guinea pig serum. No changes referable to the guinea pig serum were seen in the normal tissues or organs of mice receiving it. Mouse lymphoma cells, suspended artificially as individuals in a physiological saline solution, regularly remained viable following incubation in vitro in mixture with guinea pig serum during 6 hours at 37°C. The finding provides strong evidence that the regression of lymphomas that follows injection of guinea pig serum in vivo is brought about through some reaction in which the guinea pig serum and the host both participate. Some of the implications of the findings are discussed.

EVIDENCE THAT THE L-ASPARAGINASE OF GUINEA PIG SERUM IS RESPONSIBLE FOR ITS ANTILYMPHOMA EFFECTS

“…(2) showed that the antilymphoma activity of guinea pig serum was relatively easily destroyed b y heating; in guinea pig serum kept at 56°C slight inactivation occurred, and at 66°C this became complete. Table I I I shows the result of an experiment in which a number of samples of guinea pig serum were incubated at varying temperatures for 30 minutes.…”

“…(Received for publication, April 3, 1963) The action of guinea pig serum in bringing about in vivo, the regression of 3 transplanted mouse and rat lymphomas was first described by Kidd in papers from this laboratory in 1953 (1,2). Several highly specific features were shown: first, that inhibition was produced only by guinea pig serum, sera from other animal species being completely devoid of effect.…”

L-Asparagine degradation in saccharomyces cerevisiae: Genetic control and biochemical properties of yeast L-asparaginase

“…In 1953, Kidd (47,48) demonstrated that the growth of certain lymphomas is suppressed and regression of certain established tumors occurs when guinea pig serum is injected into mica and rats carrying the tumors. Interest in asparaginases was stimulated when it was found to be the tumor-suppressing agent in guinea pig serum (2, 6~ 7, 8,10,14,63,113).…”

Overview on L-Asparaginase

“…Very few works are available that uses Ethidium bromide as a mutagen. Amena et al [76] performed Ethidium bromide mutagenesis on L-asparaginase producing Streptomyces gulbargensis but there were no productive mutants.…”

“…[14] A study also shows that when 4% of peptone was used as nitrogen source, high enzyme production was observed in Actinomycetes and Streptomyces griseus. [76] It was observed that the quantity of nitrogen source also affected enzyme production. Liu et al [89] gave evidence that when 0.05% yeast extract medium was used no yield was observed and when the concentration was increased to 3% complete inhibition of the enzyme yield was observed.…”