Neurotoxicity of alkylated polycyclic aromatic compounds in human neuroblastoma cells

ABSTRACT

Polycyclic aromatic compounds (PAC) are ubiquitous environmental pollutants originating from incomplete combustion processes. While the toxicity of parent PAC such as benzo[a]pyrene (BaP) is well characterized, effects of other alkyl-PAC dibenzothiophene (DBT) and retene (Ret) are not well established. The aim of this study was to examine the underlying relative neurotoxic mechanisms attributed to BaP (parent PAH), DBT and Ret (alkyl-PACs) using human neuroblastoma SK-N-SH cells. The lethal concentrations (LC₁₀ and LC₂₀) were found at approximately 10 µM and 40 µM, respectively after 24-h exposure of SK-N-SH cells. It was hypothesized that PAC trigger reactive oxygen species (ROS) production, leading to activation of apoptotic signaling pathways. Differentiated neuronal cells were treated with three compounds at (0.5–40 µM) for 24 h. There was a significant concentration-dependent increase in levels of ROS, even at sub-lethal levels of 1 µM Ret. The mitochondrial membrane potential (MMP) was significantly decreased. Real-time RT-PCR results showed up-regulation of pro-apoptotic genes and down-regulation of antioxidative genes expression in BaP-, DBT-, and Ret-treated SK-N-SH cells. Cytochrome c protein levels and lipid peroxidation (LPO) were also significantly elevated in a concentration-related manner. Data demonstrated that BaP-, DBT-, or Ret-induced neuronal cell damage involved oxidative stress generation through mitochondria-mediated apoptosis pathway. Alkyl-PAC also exhibited higher potency in ROS induction and reduction of MMP than parent PAC. These findings may be important for environmental risk assessment attributed to exposure to PAC.

Declaration of interest

The authors declare that there are no conflicts of interest.

Funding

To the CREATE-REACT of the Natural Sciences and Engineering Research Council of Canada for a scholarship to Sailendra Nath Sarma and to the Canada Research Chair Program for financial support to HMC.

Additional information

Funding

To the CREATE-REACT of the Natural Sciences and Engineering Research Council of Canada for a scholarship to Sailendra Nath Sarma and to the Canada Research Chair Program for financial support to HMC.