title: Combined toxic effect of airborne heavy metals on human lung cell line A549.
abstract: Many studies have demonstrated that heavy metals existing as a mixture in the atmospheric environment cause adverse effects on human health and are important key factors of cytotoxicity; however, little investigation has been conducted on a toxicological study of a metal mixture from atmospheric fine particulate matter. The objective of this study was to predict the combined effects of heavy metals in aerosol by using in vitro human cells and obtain a suitable mixture toxicity model. Arsenic, nickel, and lead were selected for mixtures exposed to A549 human lung cancer cells. Cell proliferation (WST-1), glutathione (GSH), and interleukin (IL)-8 inhibition were observed and applied to the prediction models of mixture toxicity, concentration addition (CA) and independent action (IA). The total mixture concentrations were set by an IC10-fixed ratio of individual toxicity to be more realistic for mortality and enzyme inhibition tests. The results showed that the IA model was statistically closer to the observed results than the CA model in mortality, indicating dissimilar modes of action. For the GSH inhibition, the results predicted by the IA and CA models were highly overestimated relative to mortality. Meanwhile, the IL-8 results were stable with no significant change in immune reaction related to inflammation. In conclusion, the IA model is a rapid prediction model in heavy metals mixtures; mortality, as a total outcome of cell response, is a good tool for demonstrating the combined toxicity rather than other biochemical responses.
authors.affiliation: School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Korea.
authors.forename: Yeowool
authors.initials: Y
authors.lastname: Choi
authors.affiliation: School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Korea.|PM2.5 Research Center, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Korea.
authors.forename: Kihong
authors.initials: K
authors.lastname: Park
authors.affiliation: School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Korea.
authors.forename: Injeong
authors.initials: I
authors.lastname: Kim
authors.affiliation: School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Korea. sdkim@gist.ac.kr.
authors.forename: Sang D
authors.initials: SD
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000336:Aerosols; D000393:Air Pollutants / Q000633:toxicity*; D001151:Arsenic / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D016209:Interleukin-8 / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D019216:Metals, Heavy / Q000633:toxicity*; D008954:Models, Biological
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D016209:Interleukin-8; D019216:Metals, Heavy; D005978:Glutathione; D001151:Arsenic
keywords: Concentration addition; Heavy metals; Human cells; Independent action; Mixture toxicity