The response of L5178Y lymphoma sublines to oxidative stress: Antioxidant defence, iron content and nuclear translocation of the p65 subunit of NF-kappa B

We examined the response to hydrogen peroxide of two L5178Y (LY) sublines w hich are inversely cross-sensitive to hydrogen peroxide and X-rays: LY-R ce lls are radioresistant and hydrogen peroxide-sensitive, whereas LY-S cells are radiosensitive and hydrogen peroxide-resistant. Higher initial DNA brea ks and higher iron content (potentially active in the Fenton reaction) were found in the hydrogen peroxide sensitive LY-R cells than in the hydrogen p eroxide resistant LY-S cells, whereas the antioxidant defence of LY-R cells was weaker. In particular, catalase activity is twofold higher in LY-S tha n in LY-R cells. The content of monobromobimane-reactive thiols is 54% high er in LY-S than in LY-R cells. In contrast, the activity of glutathione per oxidase (GPx) is about two times higher in LY-R than in LY-S cells; however , upon induction with selenium the activity increases 15.6-fold in LY-R cel ls and 50.3-fold in LY-S cells. Altogether, the sensitivity difference is r elated to the iron content, the amount of the initial DNA damage, as well a s to the efficiency of the antioxidant defence system. Differential nuclear translocation of p65-NF-kappaB in LY sublines is due to the more efficient antioxidant defence in LY-S than in LY-R cells.