We investigated the role of reactive oxygen intermediates and protein kinase C in the induction of expression of the c-jun gene in human ML-2 leukemic cells and normal human DET-551 fibroblasts by comparing the effects of exposure to either ionizing radiation or H2 O2 in the presence or absence of appropriate inhibitors. In these cell types, the radiation- and H2 O2-mediated increase in c-jun mRNA levels could be prevented by pretreatment of the cells with N-acetylcysteine, an antioxidant, or H7, an inhibitor of protein kinase C and protein kinase A, but not by HA1004, a specific inhibitor of protein kinase A and G. These results suggest a role for protein kinase C and reactive oxygen intermediates in the induction of c-jun gene expression in both normal and tumor cells. We also investigated potential differences in c-jun gene expression induced by radiation or H2 O2 in normal and tumor cells by examining steady-state c-jun mRNA levels in a number of human fibroblast, leukemia, melanoma, sarcoma and carcinoma cell types. We observed heterogeneity in the steady-state level of c-jun mRNA in both the untreated normal and tumor cells and in such cells exposed to ionizing radiation or to H2 O2. Exposure to radiation produced a varied response which ranged from little or no induction to an increase in the steady-state level of the c-jun mRNA of more than two orders of magnitude. Exposure to H2 O2 gave a pattern similar to that of ionizing radiation. The basis for the differential induction in response to these agents may be attributable to either cell lineage or genetic heterogeneity or a combination of these two parameters.
Heterogeneity in c-jun Gene Expression in Normal and Malignant Cells Exposed to Either Ionizing Radiation or Hydrogen Peroxide
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Frank R. Collart, Mitsuzo Horio, Eliezer Huberman; Heterogeneity in c-jun Gene Expression in Normal and Malignant Cells Exposed to Either Ionizing Radiation or Hydrogen Peroxide. Radiat Res 1 May 1995; 142 (2): 188–196. doi: https://doi.org/10.2307/3579028
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