Mutagenicity of diesel exhaust particles mediated by cell–particle interaction in mammalian cells

Diesel exhaust particle (DEP) has been identified as a class 2A human carcinogen and closely related to the increased incidence of respiratory allergy, cardiopulmonary morbidity and mortality, and risk of lung cancer. However, the molecular mechanisms of DEP mutagenicity/carcinogenicity are still largely unknown. In the present study, we focused on the mutagenicity of DEPs in human–hamster hybrid (AL) cells and evaluated the role of cell–particle interaction in mediating mutagenic process. We found that DEPs formed micron-sized aggregates in the medium and located mainly in large cytoplasmic vacuoles of cells by 24 h treatment. The cellular granularity was increased by DEP treatment in a dose-dependent manner. DEPs resulted in a dose-dependent increase of mutation yield at CD59 locus in AL cells, while inflicting minimal cytotoxicity. There was a more than two-fold increase of mutation yield at CD59 locus in AL cells exposed to DEPs at a dose of 50 μg/ml. Such induction was significantly reduced by concurrent treatment with phagocytosis inhibitors, cytochalasin B and ammonium chloride (p < 0.05). These results provided direct evidence that DEPs was mutagenic in mammalian cells and that cell–particle interaction played an essential role in the process.