Genotoxic and protective effects of hyperbaric oxygen in A549 lung cells.
The human lung cell line A549 is frequently used as an in vitro model for studying lung toxicity and genotoxicity of environmental mutagens and carcinogens. Hyperbaric oxygen (HBO) treatment has been shown to be an excellent model for investigating the genetic consequences of oxidative stress in vitro and in vivo. We have now studied the genotoxic effects of and adaptive protection by HBO in A549 cells. Using the alkaline Comet assay, our results show that HBO exposure directly induces DNA damage but reduces the DNA-damaging effect of a second HBO treatment of the cells 24 h later. HBO pretreatment also reduces potassium chromate-induced genotoxicity in A549 cells. Heme oxygenase-1 (HO-1) protein level is increased 24 h after HBO exposure and inhibition of HO-1 activity by tin-mesoporphyrin increased HBO genotoxicity. These results are in accordance with previous findings suggesting an involvement of HO-1 in the adaptive protection. Our study indicates that A549 cells are an appropriate cell culture system for the evaluation of genetic effects induced by HBO in lung cells.
Speit
Günter
G
Universitätsklinikum Ulm, Abteilung Humangenetik, D-89070 Ulm, Germany. guenter.speit@medizin.uni-ulm.de
Bonzheim
Irina
I
D000818:Animals; D002478:Cells, Cultured; D002840:Chromates / Q000494:pharmacology; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D006931:Hyperbaric Oxygenation; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D008875:Middle Aged; D010100:Oxygen / Q000494:pharmacology*; D017680:Potassium Compounds / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology
D002840:Chromates; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D017680:Potassium Compounds; D020011:Protective Agents; C055421:tin mesoporphyrin; C027373:potassium chromate(VI); C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010100:Oxygen