Assessment of genotoxicity of four volatile pollutants from cigarette smoke based on the in vitro γH2AX assay using high content screening

To evaluate the genotoxic effects of formaldehyde, acetaldehyde, acrolein and benzene on A549 cells, the in vitro γH2AX assay was used in combination with high content screening (HCS) technology. All aldehydes showed a significant genotoxicity in a dose/time-dependent effect on the induction of γH2AX. Benzene failed to show a significant genotoxicity based on the γH2AX assay. However, hydroquinone (one of metabolites of benzene) showed a significant genotoxicity in vitro. Based on the dose-response of γH2AX and Hill model, the ability to induce DNA double-strand break can be evaluated as acrolein > formaldehyde > acetaldehyde > benzene. The slow DNA damage/repair mechanism may be more important than the fast one for aldehydes based on time-course of γH2AX and two-component model. Overall, all toxicants were genotoxic in a dose- or time-dependent manner based on the in vitro γH2AX HCS assay, and acrolein had a strong potential to induce DNA damage followed by formaldehyde, acetaldehyde and benzene in sequence.