PROOXIDANT CONDITIONS INDUCED BY DIFFERENTIAL IRON UPTAKE IN MOUSE L-CELLS

Background - The purpose of this study was to investigate the influenc e of iron metabolism on the pro-oxidant status of the cell. Methods - Studies were made on stable cell transfectants E10.5 and E10.8 derived from the LTK- cell line by transfection with human transferrin recept or (TR) cDNA bearing an intact sequence or lacking the 3' untranslated iron regulatory region, respectively. Results - The relative iron upt ake rates for these cells was E10.8>E110.5 much greater than LTK. Howe ver, the E10.5 cells exhibited the highest basal levels of 8-oxo-7,8-d ihydro-2'deoxyguanosine and of heme oxygenase mRNA, indicating that th ese cells undergo continuous oxidative stress. Although the E10.8 tran sfectant took up iron slightly faster than the E10.5 transfectant, it also accumulated almost twice as much ferritin. Apparently, the excess of iron in the E10.5 transfectant is diverted to other cellular compa rtments. In fact, DNA-bound iron in these cells was about twice as hig h as in E10.8 and LTK- cells. Conclusions - These data seem to suggest that both the rate of iron uptake and iron distribution in the cell i nfluence its pro-oxidant status.