Cytosolic protection against ultraviolet induced DNA damage by blueberry anthocyanins and anthocyanidins in hepatocarcinoma HepG2 cells.

UV-induced DNA damage plays a key role in the etiology of certain diseases. The ability of blueberry anthocyanins and anthocyanidins (BA) to protect cellular DNA from UV-induced damage was investigated. BA were extracted by water (BAW), ethanol (BAE) or methanol (BAM). These extracts partially restored proliferation of UV-irradiated HepG2 cells as shown by MTT assay. Treatment with BA extracts at 75 µg/ml decreased reactive oxygen species and decreased DNA damage by tail moment of comet assay and expression of γH2AX in situ. BAM significantly decreased gene and protein expression of p53, phospho-p53 (Ser15), and p21 in UV-irradiated HepG2 cells. BA thus efficiently protects cells from DNA damage in vitro. Blueberry may potentially be used as a good source of naturally radioprotective agents.

Protective roles of Gadd45 and MDM2 in blueberry anthocyanins mediated DNA repair of fragmented and non-fragmented DNA damage in UV-irradiated HepG2 cells.

Growth Arrest and DNA Damage-inducible 45 (Gadd45) and MDM2 proteins, together with p21 and p53, play important roles in cell cycle checkpoints, DNA repair, and genome integrity maintenance. Gadd45 and MDM2 were activated and transcribed instantly by UV irradiation, whereas blueberry anthocyanins (BA) decreased the gene and protein expression levels in HepG2 cells for up to 24 h, and gradually restored the UV-induced fragmented and non-fragmented DNA damage of the nucleus at a time point of 12 h. Nevertheless, UV-irradiated HepG2 cell arrests occurred mainly in the G1 phase, which indicated G1 as a checkpoint. The proteins, p21 and p53, retain cellular integrity, suppressing the oncogenic transformation by interruption of the G1 phase of the cellular cycle, giving time for repairing the damage to DNA, or apoptosis induction if the damage is too severe to be repaired, while MDM2 and Gadd45 concomitantly ensure the presence of p53 and p21. Thus, we conclude that repair, together with Gadd45 and MDM2 genes, were involved in light and dark reaction mechanisms, however, BA could interfere and assist the repair through restoration, although further studies of the complex of the gene cascades triggered and responded to in BA-assisted DNA repair are needed.