THE REDUCED COENZYME NICOTINAMIDE ADENINE-DINUCLEOTIDE (NADH) REPAIRSDNA-DAMAGE OF PC12 CELLS INDUCED BY DOXORUBICIN

The effect of NADH on DNA repair was investigated on PC12 cells, damag ed by doxorubicin. PC12 cells were incubated in medium without and wit h NADH before and after exposure to the DNA damaging agent doxorubicin . The changes of the cell proliferation genes (c-myc, c-erbB-2), the a poptosis inhibition gene bcl-2 and p53 (tumor suppressor gene), cell a poptosis gene (c-fos) and the proliferating cell nuclear antigen (PCNA ) were investigated using a cytotoxicity assay and immunofluorescence flow cytometric analysis. Doxorubicin induced DNA damage in PC 12 cell s by inhibiting the expression of the cell proliferation genes and by triggering apoptotic processes in the cells. This was shown by down re gulating the expression of c-erb-2, c-myc, bcl-2 and upregulating the expression of PCNA and c-fos of the PC 12 cells. NADH did not only inc rease the resistance of PC 12 cells to the doxorubicin induced DNA dam age but also repaired the damage partially. NADH promoted survival and differentiation by regulating the c-myc oncogene protein. Furthermore it supported the process of DNA repair by regulating the expression o f p53 bcl-2 on the PC12 cells damaged by doxorubicin. NADH also down r egulated expression of the cell apoptosis gene c-fos on the PC12 cells . The expression of c-erbB-2 oncogene protein and PCNA on the PC12 cel ls did not show a significant change in the group of cells incubated w ith NADH in comparison to the group incubated with medium alone. In ad dition, an abnormal proliferation effect of NADH on PC12 cells has not been observed in these experiments. For these results we conclude tha t NADH may be considered as a therapeutic adjunct for cancer patients to protect normal cells from the toxic effect of chemotherapeutic agen ts such as doxorubicin or cisplatin by stimulating the DNA repair syst em and by promoting normal cellular biosynthetic responses after chemo therapy.