Toxicological Evaluaion For Carbon Nanomaterials And Possible Mechanisms Underlying The Pulmonary Toxicity

With the development of modern science and technology, the nanotechnology has been undergone a rapidly growth all over the world. With the nanotechnologies have been used in mostly all the fields, and like most new technologies, the emphasis on benefits has been offset by considerable debate about the uses and safety of nanotechnologies. Therefore, nanoparticles draw a lot of attentions for their serious inhalation toxic effect since the nanoparticles can penetrate into lung and then can be translocated to other internal organs through different exposure pathways, such as inhalation and skin exposure.Carbon nanotubes (CNT) are an important new class of engineered materials that have numerous novel and useful properties. The increasing in manufacture makes it likely that increasing human exposure will occur. And more and more researches have confirmed that the CNT has potent hidden danger to biological systems. The possible mechanisms underlying the pulmonary toxic are also the crucial centre of the debate.The first part of our work is focus on the CNT and its microenvironment leachates. We evaluate the toxicity of the CNT and its leachates on the cell viability, intracellular reactive oxygen species (ROS), intracellular SOD content level and the cytoskeleton. We found that there are obvious time-and dose-dependent effects. The metal content has the positive relationship with the toxicity no matter the metal in the CNTs or in the leachates. We further evaluate the toxicity of the CNTs, leachates and the mixture of CNT and its leachate. All the toxic biomarkers we test is following the order:the mixture>the leachate> CNT. These data indicate that the most toxic part of the CNT is the metal, which can be leached from the CNT if the CNT is in the biological environment in a long period. The possible mechanism about the toxicity which main material is the iron content leachate has been detected. We found that the main mechanism is that the iron can go into the cell through the transferrin receptor and raise the LIP. The excessive iron can interfere the intracellular iron metabolism and raise the intracellular ROS level and damage the cells. This part has solved the problem about the metal in CNT and the CNT itself which plays an key role in the toxicity. The molecular biological methods were used to detect the possible mechanism in order to give a systematic explanation.The second part of our work is about the apoptosis mechanism that is induced by the pristine Graphene. The pristine Graphene has great capacity to induce cytotoxicity, intracellular ROS and induce apoptosis. We found that the mitogen-activated protein kinases and TGF-beta is the key to find the answer. The JNK, ERK and P-38 can be activated by the pristine Graphene, so does the SMAD signal pathway. The activated SMAD protein can drive the Bim protein and induce the Caspase3 to be activated, and then the apoptosis occurred. This research has first proven that the pristine Graphene can induce apoptosis through the MAPK and TGF-beta signal pathway. This study provides an insight for a new method to suppress the apoptosis induced by the Graphene through the MAPK and TGF-beta signal pathway in the future research. This study also highlights a good regulatory signal pathway site to control the Graphene induce cytotoxicity.