Understanding the role of nano-TiO2 on the toxicity of Pb on C.dubia through modeling-Is it additive or synergistic?

Nano-TiO_(2) can remarkably increase lead(Pb)toxicity in aquatic organisms.However,the mechanism of this toxicity,additive or synergistic,is not well understood.To explore this mechanism,we inspected the role of nano-TiO_(2) in the toxicity of Pb on Ceriodaphnia dubia(C.dubia),a model water flea species typically used for ecotoxicity studies.The effect of algae,a diet for aquatic organisms,on the effect of this binary mixture was also investigated.A two-compartment toxicokinetic(TK)-toxicodynamic(TD)modeling approach was used to quantify the Pb toxicity under these complex conditions and to develop critical parameters for understanding the mechanism of toxicity.This twocompartment modeling approach adequately described the Pb accumulation in the gut and in the rest of the body tissue under different nano-TiO_(2) concentrations,with and without algae,and predicted the toxicity response of C.dubia.It indicated that increasing the nano-TiO_(2) concentration reduced the Pb tolerance level and concurrently increased the killing rate constant of C.dubia.Therefore,nano-TiO_(2) synergistically enhanced Pb toxicity.Algae remarkably reduced the toxicity of this binary mixture through reducing the Pb transfer rate to the body tissue and the killing rate,although it did not affect the Pb tolerance level.This two-compartment modeling approach is useful in understanding the role of nanoparticles when assessing the overall toxicity of nanoparticles and other toxic elements in the environment.

Synergistic effects of particulate matter(PM_10) and SO_2 on human non-small cell lung cancer A549 via ROS-mediated NF-κB activation

Since a real atmospheric scenario usually represents a system involving multiple pollutants, air pollution studies typically focused on describing adverse effects associated with exposure to individual pollutants cannot reflect actual health risk. Particulate matter（PM10） and sulfur dioxide（SO2） are two major pollutants derived from coal combustion processes and co-existing in coal-smoke air pollution, but their potentially synergistic toxicity remains elusive thus far. In this study, we investigated the cytotoxic responses of PM10 and SO2, singly and in binary mixtures, using human non-small cell lung cancer A549 cells, followed by clarifying the possible mechanisms for their interaction. The results indicated that the concomitant treatment of PM10 and SO2 at low concentrations led to synergistic injury in terms of cell survival and apoptosis occurrence, while PM10 and SO2 alone at the same concentrations did not cause damage to the cells. Also, radical oxygen species（ROS） production followed by nuclear factor kappa B（NF-κB） activation was involved in the above synergistic cytotoxicity, which was confirmed by the repression of the actions by an ROS inhibitor（NAC）. This implies that assessment of health risk should consider the interactions between ambient PM and gaseous copollutants.