Role of N-Acetyl Cysteine and Acetyl-L-Carnitine Combination Treatment on DNA-Damage-Related Genes Induced by Radiation in HEI-OC1 Cells
Purpose: The aim of the present study was to evaluate the effect of acetyl-L-carnitine (ALC) and N-acetyl cysteine (NAC) on ionizing radiation (IR)-induced cytotoxicity and change in DNA damage-related genes in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells.
Methods: HEI-OC1 cells were irradiated with 5 Gy radiation and treated by eight combinations of NAC and/or ALC: control, NAC, ALC, IR, NAC + IR, ALC + NAC, ALC + IR, and ALC + NAC + IR. Cell viability, apoptotic cell death and DNA damage were measured at the 72nd hour. Eighty-four IR-induced DNA-damage-related genes were determined by RT-PCR gene array and >10-fold changes were considered significant.
Results: IR decreased cell viability by about 50% at 72 hours of incubation. In particular, the ALC and/or NAC combination before IR protected the HEI-OC1 cells (p < 0.05). Single and combination treatment prior to IR led to lower apoptotic cell death(p < 0.05). There was a significant lower DNA damage in ALC + NAC + IR group compared to IR group(p < 0.05).
Expressions of Brca2, Xpc, Mlh3, Rad51, Xrcc2, Hus1, Rad9a, Cdkn1a, Gadd45a which are the DNA-repair genes were found to be significant higher in NAC + ALC + IR group than those in individual treatment of ALC or NAC.
Conclusions: ALC and/or NAC treatment prior to IR led to higher cell viability and lower apoptotic cell damage compared to IR group. The results of the study show that the ALC + NAC combination treatment inhibits DNA damage and induces DNA-repair genes to repair radiation damage, and this combination treatment is more effective against radiation-induced DNA damage than NAC or ALC therapy individually.
