title: SOD2-mediated effects induced by WR1065 and low-dose ionizing radiation on micronucleus formation in RKO human colon carcinoma cells.
abstract: RKO36 cells exposed to either WR1065 or 10 cGy X rays show elevated SOD2 gene expression and SOD2 enzymatic activity. Cells challenged at this time with 2 Gy exhibit enhanced radiation resistance. This phenomenon has been identified as a delayed radioprotective effect or an adaptive response when induced by thiols or low-dose radiation, respectively. In this study we investigated the relative effectiveness of both WR1065 and low-dose radiation in reducing the incidence of radiation-induced micronucleus formation in binucleated RKO36 human colon carcinoma cells. The role of SOD2 in this process was assessed by measuring changes in enzymatic activity as a function of the inducing agent used, the level of protection afforded, and the inhibitory effects of short interfering RNA (SOD2 siRNA). Both WR1065 and 10 cGy X rays effectively induced a greater than threefold elevation in SOD2 activity 24 h after exposure. Cells irradiated at this time with 2 Gy exhibited a significant resistance to micronucleus formation (P < 0.05; Student's two-tailed t test). This protective effect was significantly inhibited in cells transfected with SOD2 siRNA. SOD2 played an important role in the adaptive/delayed radioprotective response by inhibiting the initiation of a superoxide anion-induced ROS cascade leading to enhanced mitochondrial and nuclear damages.
authors.affiliation: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Murley
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Richard C
authors.initials: RC
authors.lastname: Miller
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
authors.forename: Gayle
authors.initials: G
authors.lastname: Woloschak
authors.forename: David J
authors.initials: DJ
authors.lastname: Grdina
mesh_terms: D000222:Adaptation, Physiological; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D006801:Humans; D008624:Mercaptoethylamines / Q000494:pharmacology*; D048629:Micronuclei, Chromosome-Defective; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000528:radiation effects; D013481:Superoxides / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane