Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways

Ionizing radiation and doxorubicin both produce oxidative damage and double-strand breaks in DNA. Double-strand breaks and oxidative damage are highly toxic and cause cell cycle arrest, provoking DNA repair and apoptosis in cancer cell lines. To investigate the response of normal human cells to agents causing oxidative damage, we monitored alterations in gene expression in F65 normal human fibroblasts. Treatment with gamma-irradiation and doxorubicin altered the expression of 23 and 68 known genes, respectively, with no genes in common. Both agents altered the expression of genes involved in cell cycle arrest, and arrested the treated cells in G(2)/M phase 12 h after treatment. 24 h after gamma-irradiation, the percentage of G(1) cells increased, whereas after doxorubicin treatment the percentage of G(2)/M cells remained constant for 24 h. Our results suggest that F65 cells respond differently to gamma-irradiation- and doxorubicin-induced DNA damage, probably using entirely different biochemical pathways.