Department of Applied Life Sciences, Niigata University of Pharmacy & Applied Life Sciences, Higashijima 265-1, Niigata 956-8603, Japan.
Food Funct. 2013 Jan;4(1):63-73. doi: 10.1039/c2fo30088e. Epub 2012 Sep 19.
Antioxidant biofactor (AOB) is one of the fermented grain food supplements commercially available in Japan and other countries. Herein, we investigated the effect of AOB on the UVC (254 nm) induced DNA damage in A549 cells. Both distilled water and MeOH extracts of AOB did not show any significant cell toxicity. However, the UV (25-75 J m(-2)) induced cell death was amplified in the presence of these extracts, especially the MeOH extract. When the DNA damage was evaluated by comet assay, the AOB water extract prevented the UV induced DNA damage at the initial stage but significantly inhibited the repair process, especially in the cells exposed to a high dose of UV. The retardation of DNA repair was significantly higher in the presence of the MeOH extract, concentrating such components as caffeine and polyphenols, and thus the damage was enhanced both in the cells irradiated by low and high doses of UV. The DNA damage profile was consistent with the inhibitory profile of ATR, a key kinase of DNA damage checkpoint signaling. The AOB MeOH extract markedly reduced the phosphorylation level of the checkpoint proteins activated by UV, such as p53, SMC1 and Chk1, together with ATR. The inhibitory effect of the AOB water extract was less effective as compared to the MeOH extract, but was dose-dependent both in the cells irradiated with high and low doses of UV. The dual role of AOB as an antioxidant and a checkpoint modulator suggests its beneficial use in complementary medicine as a potential sensitizer of anticancer treatment.
抗氧化生物因子（AOB）是日本和其他国家市售的发酵谷物食品补充剂之一。在此，我们研究了 AOB 对 UVC（254nm）诱导的 A549 细胞 DNA 损伤的影响。AOB 的蒸馏水和甲醇提取物均没有显示出明显的细胞毒性。然而，在这些提取物的存在下，UV（25-75J m(-2))诱导的细胞死亡被放大，尤其是甲醇提取物。当通过彗星试验评估 DNA 损伤时，AOB 水提取物在初始阶段阻止了 UV 诱导的 DNA 损伤，但显著抑制了修复过程，尤其是在暴露于高剂量 UV 的细胞中。在存在甲醇提取物的情况下，DNA 修复的延迟更为明显，浓缩了咖啡因和多酚等成分，从而在低剂量和高剂量 UV 照射的细胞中增强了损伤。DNA 损伤谱与 ATR 的抑制谱一致，ATR 是 DNA 损伤检查点信号的关键激酶。AOB 甲醇提取物显著降低了由 UV 激活的检查点蛋白的磷酸化水平，如 p53、SMC1 和 Chk1 以及 ATR。与甲醇提取物相比，AOB 水提取物的抑制作用效果较差，但在高剂量和低剂量 UV 照射的细胞中均呈剂量依赖性。AOB 作为抗氧化剂和检查点调节剂的双重作用表明，它作为一种潜在的癌症治疗增敏剂，在补充医学中有其有益的用途。
