Aflatoxin G1-induced oxidative stress causes DNA damage and triggers apoptosis through MAPK signaling pathway in A549 cells.

Abstract

Our previous studies showed that Aflatoxin G1 (AFG1) could induce lung adenocarcinoma, and that the cancer cells originated from alveolar type II cells (AT-II cells). Recently, we found AFG1 induced structural impairment in rat AT-II cells, which may account for an early event in lung tumorigenesis. However, the mechanism of AFG1-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 AFG1 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 AFG1 induced oxidative stress by increasing ROS generation and caused DNA double-strand breaks (DSBs) by up-regulating γH2AX expression. AFG1 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 AFG1-treated cells. Furthermore, we found AFG1 activated ROS-mediated JNK and p38 pathways to induce cell apoptosis in A549 cells. In conclusion, our results indicate that AFG1 induces oxidative DNA damage and triggers apoptosis through ROS-mediated JNK and p38 signaling pathways in A549 cells, which may contribute to AFG1-induced AT-II cell damage.

• Authors: Haitao Shen, Jing Liu, Yuan Wang, Hongguang Lian, Juan Wang, Lingxiao Xing, Xia Yan, Junling Wang, Xianghong Zhang
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 62 Pg. 661-9 (Dec 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 24090735 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Aflatoxins
• BAX protein, human
• Reactive Oxygen Species
• bcl-2-Associated X Protein
• aflatoxin G1
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Caspase 3
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Aflatoxins (toxicity)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• DNA Damage (drug effects)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• bcl-2-Associated X Protein (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)