Abstract
In this study we examined the radiation survival response of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells (BEAS-2B) stably transfected with c-raf-1 and/or c-myc.C-raf-1 transfectants (2B-raf), and c-raf-1andc-mycdouble transfectants (2B-raf/myc) were relatively radioresistant compared with c-myc(2B-myc) or control vector transfectants (2B-neo) (2B-raf,D0= 2.445 Gy; 2B-raf/myc,D0= 2.46 Gy; 2B-myc,D0= 1.501 Gy; 2B-neo, D0= 2.029 Gy). The steady state level of superoxide dismutase (SOD) mRNA was higher in radioresistant cells (2B-rafand 2B-raf/myc). In addition, 2B-rafbut not 2B-raf/mycor 2B-myc transfectants revealed relatively higher number of cells in G2+M phase of the cell cycle. These findings present experimental evidence that Raf-1 expression correlates with the radiation-resistant response of 2B-rafor 2B-raf/myctransfectants and suggest a role of SOD in Raf-1-associated radiation resistance. Because 2B-raftransfectants are non-tumorigenic, and double transfectants (2B-raf/myc) are tumorigenic with some phenotypic traits found in small-cell lung carcinomas, our data imply a dissociation between the Raf-1-mediated mechanisms of radiation protection and progression of lung neoplasia.
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