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The cellular defense system (including glutathione, glutathione-related enzymes, antioxidant and redox enzymes) plays a crucial role in cell survival and growth in aerobic organisms. To understand its physiological role in tumor cells, the glutathione con-tent and related enzyme activities in the human nor-mal hepatic cell line, Chang and human hepatoma cell line, HepG2, were systematically measured and com-pared. Superoxide dismutase, catalase, and glutathione peroxidase activities are 2.8-, 4.3-, and 2.9-fold higher in HepG2 cells than in Chang cells. Total glutathione content is also about 1.4-fold higher in HepG2, which is supported by significant increases in γ-glutamylcy-steine synthetase and glutathione synthetase activities. Two other glutathione-related enzymes, glutathione reductase and γ-glutamyltranspeptidase, are up-regulated in HepG2 cells. However, thioredoxin reduc-tase and glutathione S-transferase activities are sig-nificantly lower in HepG2 cells. These results propose that defense-related enzymes are largely modulated in tumor cells, which might be linked to their growth and maintenance.