H. Sauri et al., CHARACTERIZATION OF AN OXIDATION-RESISTANT TUMOR-CELL LINE AND ITS SENSITIVITY TO IMMUNE-RESPONSE AND CHEMOTHERAPY, The Journal of surgical research, 58(5), 1995, pp. 526-535
Aerobic cells have several scavenger systems for protection from react
ive oxygen species (ROS). We developed an ROS-resistant variant of the
human erythroleukemic cell line K562 by culturing cells in glucose ox
idase to produce hydrogen peroxide. Testing the activity of the scaven
ger systems for ROS showed these cells had a 25- to 28-fold increase i
n catalase activity. We therefore termed this variant cell line K562-C
AT. There was no similar increase in glutathione content or activity o
f superoxide dismutase and glutathione peroxidase. To determine what e
ffect the increased catalase activity would have on the immune respons
e to these tumor cells, we compared K562 and K562-CAT sensitivity to t
umor necrosis factor-alpha (TNF alpha) activated polymorphonuclear neu
trophil (PMN), natural killer (NK), and lymphokine-activated killer (L
AK) cells. K562-CAT showed a significant increase in resistance to TNF
alpha-activated PMN but not to NK or LAK, confirming the role of ROS
in the former but not the latter. We also tested K562-CAT sensitivity
to cisplatin and mitomycin C, agents known to involve ROS in their cyt
otoxic mechanism. There was no increased resistance in K562-CAT compar
ed to parental K562, indicating that catalase is not involved in tumor
cell resistance to those drugs. Given the characteristics of its resi
stance to the immune response, K562-CAT or a similar catalase-hyperexp
ressing cell line could be useful in determining the significance of T
NF alpha-activated PMN in antitumor defenses. (C) 1995 Academic Press,
Inc.