Cells expressing FNR and Fld showed reduced oxidative damage of lipids indicating that the protection is probably exerted through an antioxidative action towards H2O2. Even though a mechanism of protection through repair can not be discarded and it has been observed for iron-sulfur centers of hydro-lyases in FNR-overexpressing bacterial cells after oxidative stress induction, FNR and Fld are not repairing enzymes per se. However, it is possible that some repairing pathways are working more efficiently in cells expressing FNR and Fld because they are more protected by the actions of these two proteins. This observation reinforces the hypothesis that oxidative stress persists 24 h after induction by hydrogen peroxide. MDA levels were much higher for Cos-7 than Cos-7/pcDNA3 cells. This difference is not really surprising as Cos-7 cell line has a faster rate of growth than all the transfected lines when grown in the presence of G418. Faster growing cells are metabolically more active and, as a consequence, more susceptible to damages by exposure to cytotoxic compounds. Given this observation, we considered important to include both lines as controls in this study to be able to discriminate between the effects of the expression of FNR and Fld per se and including other factors of the process of transfection and selection. Both controls are necessary to allow comparison in the case transfection or transduction systems different from the one used here were employed. The protection from hydrogen peroxide-induced damage resulted of similar magnitude for FNR and Fld. This finding was not expected a priori because FNR and Fld are enzymes with different properties regarding kinetics and, most probably, specificity of interactions with endogenous cellular components. We have measured the diaphorase activity of Cos-7/pFNR and found that it doubles that of the control line Cos-7/pcDNA3 supporting the idea that FNR is functional and elevates basal levels of this enzymatic activity. For Fld we do not have an estimation of the expression of this protein. MTT reduction and LPO were analyzed under MV induced injury. Cells demonstrated a major reduction in viability/growth and almost duplication of LPO content but we could not see any protection in cells expressing FNR and Fld. These findings were surprising since both FNR and Fld have shown to protect a number of eukaryote and prokaryote organisms from MV exposure. Shimizu et al. showed protection from MV damage in Cos-7 cells overexpressing oxidized protein hydrolase. This finding does not exclude, however, that changes associated with the HhAntag691 overexpression of FNR and/or Fld may result in the lack of protection we observed. Other authors using MV to induce oxidative stress have observed that protective enzymes work better if their expression is directed to mitochondria when compared with cytosolic localization. MLS in Cos-7/pFld has not been efficiently excised but this fact did not avoid protection from H2O2.