Cytotoxicity induced by the mixture components of nickel and poly aromatic hydrocarbons

Although particulate matter (PM) is composed of various chemicals, investigations regarding the toxicity that results from mixing the substances in PM are insufficient. In this study, the effects of low levels of three PAHs (benz[a]anthracene, benzo[a]pyrene, and dibenz[a,h]anthracene) on Ni toxicity were investigated to assess the combined effect of Ni-PAHs on the environment. We compared the difference in cell mortality and total glutathione (tGSH) reduction between single Ni and Ni-PAHs co-exposure using A549 (human alveolar carcinoma). In addition, we measured the change in Ni solubility in chloroform that was triggered by PAHs to confirm the existence of cation-π interactions between Ni and PAHs. In the single Ni exposure, the dose-response curve of cell mortality and tGSH reduction were very similar, indicating that cell death was mediated by the oxidative stress. However, 10 μM PAHs induced a depleted tGSH reduction compared to single Ni without a change in cell mortality. The solubility of Ni in chloroform was greatly enhanced by the addition of benz[a]anthracene, which demonstrates the cation-π interactions between Ni and PAHs. Ni-PAH complexes can change the toxicity mechanisms of Ni from oxidative stress to others due to the reduction of Ni²⁺ bioavailability and the accumulation of Ni-PAH complexes on cell membranes. The abundant PAHs contained in PM have strong potential to interact with metals, which can affect the toxicity of the metal. Therefore, the mixture toxicity and interactions between diverse metals and PAHs in PM should be investigated in the future.