Although ROS has been linked to apoptosis, DNA damage, and carcinogenesis, the role of enhanced ROS production by silica in silica-induced carcinogenesis is not completely understood. The goal of this study was to compare selleck inhibitor freshly fractured and aged silica-induced molecular alterations in human immortalized/transformed bronchial epithelial cells (BEAS-IIB) and lung cancer cells with

altered (H460) or deficient (H1299) p53 expression. Exposure to freshly fractured or aged silica produced divergent cellular responses in certain downstream cellular events, including ROS production, apoptosis, cell cycle and chromosomal changes, and gene expression. ROS production increased significantly following exposure to freshly fractured silica compared to aged silica in BEAS-IIB and H460 cells. Apoptosis showed a comparable enhanced level of induction with freshly fractured or aged silica in both cancer lines with p53 functional changes. p53 protein was present in the BEAS-IIB and was absent in cancer cell lines after silica exposure. Exposure to freshly fractured silica also resulted in a rise in aneuploidy in cancer cells with a significantly greater

increase in p53-deficient cells. Cytogenetic analysis demonstrated increased metaphase spreads, chromosome breakage, rearrangements, AS1842856 cost and endoreduplication in both cancer cells. These results suggest that altered and deficient p53 affects the cellular response to freshly fractured silica exposure, and thereby enhances susceptibility and augments Benzatropine cell

proliferation and lung cancer development.”
“Predicting chronic exposure to air pollution at the intra-urban scale has been recognized as a priority area of research for environmental epidemiology. Exposure assessment models attempt to predict and proxy for individuals’ personal exposure to ambient air pollution, and there are no studies to date that explicitly attempt to compare and cross-validate personal exposure concentrations with pollutants modeled at the intra-urban level using methods such as interpolated surfaces and land-use regression (LUR) models. This study aimed to identify how well personal exposure to NO(2) (nitrogen dioxide) can be predicted from ambient exposure measurements and intra-urban exposure estimates using LUR and what other factors contribute to predicting variations in personal exposure beyond measured pollutant levels within home. Personal, indoor and outdoor NO(2) were measured in a population of older adults (>65 yr old) living in Hamilton, Canada. Our results show that personal NO(2) was most strongly associated with contemporaneously collected indoor and outdoor concentrations of NO(2). Predicted NO(2) exposures from intra-urban LUR models were not associated with personal NO(2), whereas interpolated surfaces of particulates and ozone were modestly associated.