Identification of genes responsible for DNA damage induced senescence

Cellular senescence is defined as permanent growth arrest induced by various stresses. Although the transcriptional activity of p53 is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. We developed an experimental system in which either senescence or apoptosis is specifically induced in the same cell line (hepatocarcinoma HepG2 cells having the intact p53 gene) by altering concentrations of a DNA-damaging drug and compared gene expression profiles by using microarray analysis to distinguish genes specific for senescence from those universally respond to DNA damage. When we compared the expression profiles at low versus high doses of etoposide, 20 genes were found to be differentially upregulated by more than 2-fold at a low dose of etoposide, which are expected to function in senescence induction. Microarray results were further confirmed by qPCR. DNA damage induced gene expression in human HepG2 cells was measured at 30 hours after treatment with etoposide at 0, 10, and 100 uM.