MAPK/AP-1 and ROS participated in ratio- and time-dependent interaction effects of deoxynivalenol and cadmium on HT-29 cells

Deoxynivalenol (DON) and cadmium (Cd) not only share target organs, but also share certain upstream and downstream toxic pathways. DON and Cd may accumulate in the food chain, increasing the risk of joint exposure. Therefore, there is a significant need to characterize the joint toxicity of these two compounds. The goal of this work was to investigate the toxic trends and interaction effects of DON and CdCl2 on HT-29 cells, and uncover a role of the MAPK/AP-1 and oxidative stress pathways. The experiment was designed based on the average exposure situation in real life (DON: CdCl2, ppm: ppm, 1.62:1) and commonly used designs in toxicology research (IC50: IC50, 12/24/48 h). We observed time-, and ratio-dependent toxicity and joint effects in mixtures of CdCl2 and DON. At the plausible intestinal level, the ratio of IC50: IC50 transitioned from synergism to antagonism with increased exposure time, while the other ratio showed differential behavior. Long-term or low-dose exposure mainly resulted in antagonism, while short-term or high-dose treatment mainly resulted in synergism. The change trends of MAPK/AP-1 and oxidative stress were consistent with the cytotoxicity trend, and activation of AP-1 was confirmed by transfection assay.