Antioxidant enzymes and survival of normal and simian virus 40-transformed mouse embryo cells after hyperthermia.
Relative cell survival and activity of the free radical scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase were measured in cloned normal (MEA) and SV40-transformed (SVMEA) mouse embryo cells exposed at 44 degrees C for 0-3 h. At 37 degrees C, all three enzymes were 2-5 times higher in MEA than in SVMEA. Hyperthermia did not significantly alter enzyme levels in either cell line but selectively reduced transformed cell survival to less than 5% while relative survival of normal cells remained above 75%. The latter, however, could be reduced to 25% when normal cells were pretreated with 3 mM diethyldithiocarbamate, an inhibitor of copper- and zinc-containing superoxide dismutase. Similar treatment rendered SVMEA extremely thermosensitive. On the other hand, sublethal heat treatment (15 min at 45 degrees C) of cultured cells resulted in a relative thermal resistance upon subsequent exposure to 45 degrees C for 1-4 h. This induced thermotolerance was associated with a rise in antioxidant enzyme levels and both became significant only 4-6 h after the initial heat treatment. Induced enzyme and thermotolerance levels in transformed cells remained, nonetheless, far below those of normal cells. The data show that inherent (in MEA) as well as induced (in SVMEA) thermotolerance is associated with high antioxidant enzyme levels while the reverse is true in the case of inherent (in SVMEA) and induced (in MEA) thermosensitivity. These findings suggest that increased production of oxygen free radicals may be involved in hyperthermic cell injury, which then becomes a function of basal or inducible levels of antioxidant enzymes. Induction of the latter by hyperthermia is apparently inefficient in transformed cells making them more vulnerable. Enzyme induction seems also to require a lag period of 4-6 h suggesting the possible involvement of an intermediate inducer(s) at molecular level. The so-called heat shock proteins may be candidates for such a role.
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D004050:Ditiocarb / Q000494:pharmacology; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000502:physiology; D006979:Hyperthermia, Induced; D051379:Mice; D013539:Simian virus 40; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005609:Free Radicals; D006360:Heat-Shock Proteins; D004050:Ditiocarb; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase