(A) Effect of AOX1 alone and with the combination of AF4, Q, or Q3G on various DDR signaling proteins exposed to NNKOAc was assessed by Western blotting. (B–H) The relative amount of each protein expression level (p-ATM, p-ATR, p-Chk2, p-Chk1, p-P53, p-BRCA1, and p-γ-H2AX) with respect to the beta-actin loading control. Experimental values presented as mean ± SD of n = 3 independent experiments by one-way analysis of variance performed with Tukey’s pairwise comparison. The sign “a,b,c,d, and e” refers to statistical difference (p ≤ 0.05). All the treatment groups were compared with the DMSO control. Means that share the same letter are not significantly different at p ≤ 0.05. Pre-exposure to AOX1 with or without AF4, Q, or Q3G significantly (p ≤ 0.05) reduced the protein expression levels of DDR in BEAS-2B cells compared to NNKOAc-exposed cells. Abbreviations: AF4: apple peel flavonoid fraction 4, AOX1: antioxidant formulation, NNKOAC: 4-[(Acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanone, Q: quercetin, Q3G: Q-3-O-d-glucoside (Q3G).