Mechanisms of cellular resistance to hydrogen peroxide, hyperoxia, and 4-hydroxy-2-nonenal toxicity: the significance of increased catalase activity in H2O2-resistant fibroblasts.
An H2O2-resistant variant (OC14) of the HA1 Chinese hamster fibroblast cell line which demonstrates a 20-fold increase in catalase activity was utilized in the study of mechanisms responsible for cellular resistance to hydrogen peroxide, oxygen, and 4-hydroxy-2-nonenal toxicity. HA1 and OC14 cells were treated with 9 mM aminotriazole which resulted in a 60 to 80% reduction in catalase activity. Pretreatment with aminotriazole resulted in significant sensitization to the toxicity of 1-h exposures to exogenously applied H2O2, which was proportional to the reduction in catalase activity. Treatment with aminotriazole produced significant sensitization to the toxicity of 95% O2 after 45 h of O2 exposure but no sensitization to the toxicity of a 1-h exposure to 50 microM 4-hydroxy-2-nonenal. Inhibition of catalase activity by aminotriazole had no effect on the metabolism of 4-hydroxy-2-nonenal by either cell line tested. These results support the conclusion that in H2O2-resistant cells, catalase activity is a major determinant of cellular resistance to H2O2 toxicity, whereas catalase activity has a limited role in cellular resistance to an acute exposure to 95% O2 and is unrelated to cellular resistance to 4-hydroxy-2-nonenal.
Spitz
D R
DR
Department of Pediatrics, University of Virginia, Charlottesville 22908.
Adams
D T
DT
Sherman
C M
CM
Roberts
R J
RJ
D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants; D002374:Catalase / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D010100:Oxygen / Q000633:toxicity*; D013379:Substrate Specificity
D000447:Aldehydes; D000975:Antioxidants; D003470:Culture Media; D006861:Hydrogen Peroxide; D002374:Catalase; C027576:4-hydroxy-2-nonenal; D010100:Oxygen; D000640:Amitrole