Abstract 3815: Cellular oxidative stress and immunological effects of carbon-based nanomaterials towards lung carcinogenicity

Abstract

Abstract Lung cancer accounts for most number of cancer related death, reporting over 26.5% of all cancer deaths in United States alone. Among the risk factors, along with smoking, occupational as well as environmental exposure of carcinogens is considered as major driver of lung cancer in most cases. In that context, high aspect ratio nanomaterials (HARNs) with low density, such as carbon nanotubes (CNTs), remain efficient air-borne particulate matters during every step of their life cycle, from production to usage to disposal. Consequently, inhalation and potentially carcinogenic nanomaterial exposure to pulmonary tissues are anticipated, which may considerably facilitate lung cancer occurrence and mortality. Apart from pulmonary interaction, nanomaterial exposure via skin or oral route may play a significant role in adverse human health effects, especially when the use of nanomaterials in food and cosmetic industries are growing exponentially. CNTs are made of flat sheets of sp2 hybridized carbon atoms layered in hexagonal geometry that are rolled into unified cylindrical structures. CNTs are subdivided into single-walled (SWCNT), double-walled (DWCNT), or multi-walled carbon nanotube (MWCNT) based on the number of carbon layers in nanotubes. Size of CNTs can range from one to several nanometers in diameter and up to several micrometers in length, exhibiting a fibrous-like length-to-width (aspect) ratio similar to asbestos fibers and potentially harbor asbestos-like pulmonary fibrosis and lung cancer risks associated with their long-term exposure. Considerable efforts has been made to study Nano-toxicity but how cellular toxicological and immunological responses are affected by nanomaterial exposure is largely unknown. The present study investigated the effects of different CNT exposure on cellular proliferation, uptake, oxidative stress, DNA damage, Stem cell-like properties along with activation of cellular innate immune responses of human lung epithelial cells and immune cells to determine the underlying cross-talks. Using a physiologically relevant long-term-low-dose exposure model, we found that both single-walled and multi-walled carbon nanotubes, induced particle-specific cellular proliferation, tumor sphere formation, reactive oxygen species (ROS) and super oxide (SO), DNA-strand breaks, mitochondrial depolarization and reduced apoptosis, indicating the genotoxicity and carcinogenic potential of CNTs. We also determined distinct immune activation signature in these cells upon CNTs exposure that closely resembles “immune mediated” carcinogenesis signature as reported in “Inflammatory Cancer (C3)” subtypes. Finally, through in silico analyses and validation we have determined potential CNT exposure induced immune effectors to devise better targeted therapeutic intervention against nanomaterial exposure induced carcinogenesis. Citation Format: Rajib Ghosh, Liying W. Rojanasakul, Yon Rojanasakul. Cellular oxidative stress and immunological effects of carbon-based nanomaterials towards lung carcinogenicity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3815.