Multi-walled carbon nanotubes inhibit potential detoxification of dioxin-mediated toxicity by blocking the nuclear translocation of aryl hydrocarbon receptor

Abstract

Despite numerous studies on effects of environmental accumulation of nano-pollutants, the influence of nanoparticles on the biological perturbations of coexisting pollutants in the environment remained unknown. The present study aimed at elucidating the perturbations of six environmental nanoparticles on detoxification of dioxin-induced toxicity at cellular level. We discovered that there was no remarkable difference in the cell uptake and intracellular distributions of these six nanoparticles. However, they have different effects on the detoxification of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Multi-walled carbon nanotubes (MWCNTs) inhibited the translocation of aryl hydrocarbon receptor (AhR) from cytosol to the nucleus, leading to the downregulation of cytochrome P450 family 1 subfamily A member 1 (CYP1A1) and inhibition of detoxification function. These findings demonstrate that MWCNTs can impact the potential detoxification of dioxin-induced toxicity through modulating AhR signaling pathway. Co-exposures to MWCNTs and dioxin may cause even more toxicity than single exposure to dioxin or MWCNTs alone.

Keywords: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD); Aryl hydrocarbon receptor; CYP1A1; Drug metabolism; Multi-walled carbon nanotubes; ROS.