Although radiation therapy is one of the choices to treat cancers and is an excellent local treatment method, existence of radiation resistant cell is a major problem. We established clinically relevant radioresistant (CRR) cells that can survive exposing to 2 Gy/day X-rays for more than 30 days. However, the mechanism to obtain resistance has not been elucidated yet. We investigated the relationships between resistant mechanism to hydrogen peroxide (H₂O₂) and plasma membrane state in CRR cells.
　CRR cells showed resistance to H₂O₂, but catalase enzyme activity was down-regulated. Plasma membrane potential were low, no internal H₂O₂ increase and no lipid peroxidation were seen even after 2 hours of H₂O₂ treatment in CRR cells. Administration of oxidized lipid led to further cell death after H₂O₂ treatment in CRR cells. The lipoxygenase (ALOX) gene and protein expressions were down-regulated in CRR cells. We also established stress-sensitive ρ⁰ cells that lack mitochondrial DNA. Gene and protein expressions of ALOX were up-regulated in ρ⁰ cells. Expression of cyclooxygenase-2 does not seem to be involved in this mechanism.
　These results suggest that the involvement of ALOX in resistance or sensitivity of cancer treatment.