Cells transfected with transferrin receptor cDNA lacking the iron regulatory domain become more sensitive to the DNA-damaging action of oxidative stress.

Abstract

Chinese hamster V79 cells were transfected with human transferrin receptor cDNA, lacking the 3' untranslatable regulatory sequence. One of the clones obtained was investigated completely. It exhibited the cDNA sequences recombined into the genome, transcribed the corresponding mRNA and became partially constitutive in iron uptake from transferrin. The rate of iron uptake was significantly higher in these cells than in the parental ones, as was the intracellular iron content, assessed indirectly by measuring the activation of the regulatory protein responsible for iron homeostasis control. The transfected cells were more sensitive to the DNA-damaging action of H2O2. This corroborates the important role that iron plays as a mediator of DNA damage by reactive oxygen species. It also points to the possibility that mutations at the regulatory sequences of transferrin receptors, leading to partial disturbance in iron homeostasis, might render the cells more prone to further mutations and malignant transformations by reactive oxygen species.