Aflatoxin G(1)-induced oxidative stress causes DNA damage and triggers apoptosis through MAPK signaling pathway in A549 cells

作者：Shen Haitao; Liu Jing; Wang Yuan; Lian Hongguang; Wang Juan; Xing Lingxiao; Yan Xia; Wang Junling; Zhang Xianghong^*

来源：Food and Chemical Toxicology, 2013, 62: 661-669.

DOI：10.1016/j.fct.2013.09.030

• Aflatoxin
• Alveolar type II cells
• Oxidative stress
• Apoptosis
• Mitogen-activated protein kinases

Our previous studies showed that Aflatoxin G(1) (AFG(1)) could induce lung adenocarcinoma, and that the cancer cells originated from alveolar type II cells (AT-II cells). Recently, we found AFG(1) induced structural impairment in rat AT-II cells, which may account for an early event in lung tumorigenesis. However, the mechanism of AFG(1)-induced AT-II cell damage remains unclear. DNA damage and apoptosis induced by oxidative stress are well accepted causes of cell damage. Thus, we explore whether AFG(1) activates the reactive oxygen species (ROS)/MAPK/apoptosis pathway to cause cell damage in human AT-II cells like the cell line (A549). We found AFG(1) induced oxidative stress by increasing ROS generation and caused DNA double-strand breaks (DSBs) by up-regulating gamma H2AX expression. AEG(1) also triggered apoptosis in A549 cells by regulating Fas/FasL, caspase-8, Bax, Bcl-2, and activating caspase-3. Pre-treatment with antioxidant N-acetyl-L-cysteine (NAC) reduced ROS generation and DNA DSBs, inhibited apoptosis, and increased cell viability in AFG(1)-treated cells. Furthermore, we found AFG(1) activated ROS-mediated JNK and p38 pathways to induce cell apoptosis in A549 cells. In conclusion, our results indicate that AFG, induces oxidative DNA damage and triggers apoptosis through ROS-mediated JNK and p38 signaling pathways in A549 cells, which may contribute to AFG(1)-induced AT-II cell damage.

• 出版日期2013-12
• 单位河北医科大学