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Altered glutathione metabolism in the tumor-bearing state
D Blumberg1, S Hochwald, J Pinto
1Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Background:
Because glutathione (GSH) appears to be important for tumor growth and many tumors contain the capacity (gamma-glutamyltranspeptidase) to transport GSH, we examined GSH metabolism in MCA sarcoma-bearing rats (TB).
Methods:
Tumor, liver skeletal muscle, kidney, and serum were collected from 47 MCA sarcoma (TB) rats and 26 normal (CTL) rats. Amino acids, GSH, gamma-glutamylcysteine synthetase (GCS), and gamma-glutamyl transpeptidase (GGTP) were determined.
Results:
Significant activity of GGTP (117.8 +/- 16.0 mU/min/mg protein) was present in tumors. Liver GCS activity (nanomolar per hour per milligram protein) in TB rats (106.6 +/- 37.7) was increased (p < 0.01) compared with CTL rats (57.5 +/- 12.3) and correlated positively with tumor burden (R = 0.77). Muscle GGTP was decreased (p = 0.001) in TB rats (1.7 +/- 1.1) compared with controls (6.8 +/- 1.1). Serum GSH concentrations (microM) were lower (p < 0.05) in TB rats (14.97 +/- 1.72) versus control rats (16.82 +/- 1.54) and correlated negatively with tumor burden (R = -0.83).
Conclusions:
In this tumor-bearing model, tumor has significant capacity (GGTP) for the uptake of GSH. Serum GSH is depleted in TB rats and correlates negatively with tumor burden. Liver GCS is increased in TB rats and skeletal muscle GGTP is decreased, which may preferentially benefit the tumor by increasing the bioavailability of glutathione for its own use.