Genotoxicity analysis of five particle matter toxicants from cigarette smoke based on γH2AX assay combined with Hill/Two-component model.

To investigate the genotoxic characteristics of typical toxicants in particle phase of cigarette smoke, including B[a]P, nicotine, tar, NNN and NNK. The in vitro γH2AX assay was used to detect the DNA double-strand breaks (DSBs) in A549 cells using high content screening (HCS). The results showed all toxicants had a dose/time-dependent effects on induction of γH2AX except for NNN and NNK. Based on dose-response of γH2AX and Hill model, the ability to induce DSBs was evaluated: NNN-acetate > B[a]P > NNK-acetate > tar > nicotine. Based on time-course of γH2AX and two-component model, the complex DNA damage was the main subtypes of DNA damage induced by these toxicants. Overall, all toxicants were genotoxic in A549 cells in a dose- or time- dependent manner except for NNN and NNK based on the γH2AX HCS assay. NNN-acetate had more potential to induce DSBs, which was followed by B[a]P, NNK-acetate, tar and nicotine. [ABSTRACT FROM AUTHOR]