Tryptophan degradation in transplanted tumor cells undergoing rejection.

Abstract

The depletion of an essential amino acid, tryptophan, caused by indoleamine 2,3-dioxygenase induction in vitro, has been shown to be due to a mechanism that is used in self-defense against inhaled microorganisms and tumor growth. In this communication, we report the results of measuring dioxygenase activity in the peritoneal exudate cells and tumor cytotoxicity at the transplantation loci after in vivo transplantation of tumor cells into the peritoneal cavity of syngeneic or allogeneic strains of mice. The enzyme was induced only when the tumor cells were being rejected from allogeneic animals and no change was observed when the cells continued to grow in syngeneic animals. Furthermore, when the syngeneic tumor cells in a diffusion chamber were i.p. transplanted simultaneously with i.p. injection of allogeneic tumor cells, the enzyme was induced not only in allografted tumor cells but also in the syngeneic tumor cells. Under these conditions, the tumor cells in the diffusion chamber ceased to grow and 50% of the cells were rejected. To determine the type of cells containing the induced enzyme, the peritoneal exudate cells (tumor cells and host cells--mostly small lymphocytes) were separated into six fractions by sedimentation under gravity and by differential centrifugation. Approximately 80% of total enzyme activity was localized in a tumor-rich fraction (98.9% purity), whereas only 0.2% of the activity was found in a lymphocyte-rich fraction (99.5% purity). The localization of indoleamine 2,3-dioxygenase in the tumor cells was confirmed by complement-dependent lysis with specific antibodies against tumor and host cells.

The Role of the Placental Enzyme Indoleamine 2,3-Dioxygenase in Normal and Abnormal Human Pregnancy

“…One tissue with particularly high activity is the human placenta [2]. Although the precise physiological roles of IDO are still unknown, the enzyme is induced under pathological conditions including virus infection [20], parasitic infestation [21], and tumor transplantation into allogenic animals [22,23], resulting in the rapid degradation of tryptophan to kynurenine in the infected or the tumor cells. Interferon-γ, which has potent immunomodulatory and antiproliferative effects, strongly induces the expression of the gene encoding IDO [24].…”

Activation of the Kynurenine Pathway and Production of Inflammatory Cytokines by Astrocytes and Microglia Infected WithNeospora caninum

“…18,19 Trp catabolism is also activated by interferon gamma (IFN-γ), a pro-inflammatory cytokine with a biological significance in anti-parasitic mechanisms that does not involve oxidative stress. 20,21 The multiple actions of Trp catabolites have also been related to the triggering of several neuropsychiatric disorders and make them potentially useful as biomarkers of these pathologies. 22 The present work evaluated the infection of primary cultures of rat glial cells by N. caninum through the catabolism of tryptophan, the level of inflammatory mediators and the impact of the infection on the integrity of the neural tissue.…”

L-Tryptophan Depletion Using a New Bioreactor: A Possible New Cancer Therapy

“…Besides Trp certain amino acids such as L-asparagine, and L-glutamine have been recognized as important cancer nutrients, and the removal of these amino acids can lead to decrease and destruction of the tumor [34][35][36][37]. Since these so-called anti-tumor enzymes are derived from bacterial or fungal sources, immunological responses are observed after parenteral administration [31].…”