Tryptophan degradation in transplanted tumor cells undergoing rejection.
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.
Yoshida
R
R
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Park
S W
SW
Yasui
H
H
Takikawa
O
O
D000818:Animals; D001202:Ascitic Fluid / Q000201:enzymology; D002455:Cell Division; D004790:Enzyme Induction; D006084:Graft Rejection; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010105:Oxygenases / Q000096:biosynthesis; D010529:Peritoneal Cavity / Q000201:enzymology / Q000473:pathology; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase
D014364:Tryptophan; D010105:Oxygenases; D014366:Tryptophan Oxygenase