Transient peak of p53 induction persists at low radiation doses in MCF-7 cells.

BACKGROUND: The p53 protein is a central tumour suppressor regulating numerous genes involved in cell cycle control, DNA repair, and apoptosis. Mutations in p53 occur in over half of all cancers, disrupting these regulatory pathways and enhancing tumour progression. Many cell lines, including MCF-7 breast cancer cells, exhibit oscillatory p53 and MDM2 activity, a phenomenon linked to radiosensitivity and the cellular response to ionizing radiation.

METHODS AND RESULTS: We investigated the dose-dependent dynamics of p53 activation in MCF-7 cells exposed to γ-radiation in the dose range of 0.1 to 8 Gy. Using western blot analysis and real-time quantitative PCR, we examined dynamics of the expression of p53 and its downstream targets, including CDKN1A, GADD45A, and MDM2 genes. Our findings reveal that while oscillations in p53 and its downstream targets are prominent at high radiation doses, transient peak expression persists even at doses as low as 0.1 Gy, though with delayed onset and diminished amplitude.

CONCLUSIONS: The results extend the knowledge on p53 dynamics down to 0.1 Gy. They challenge the previous models that predicted the absence of oscillations at low radiation doses.