title: Mutagenicity of diesel exhaust particles mediated by cell-particle interaction in mammalian cells.
abstract: 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 (A(L)) 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 24h 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 A(L) cells, while inflicting minimal cytotoxicity. There was a more than two-fold increase of mutation yield at CD59 locus in A(L) cells exposed to DEPs at a dose of 50mug/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.
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Hefei, PR China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Bao
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Chen
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Wu
authors.forename: Zengliang
authors.initials: Z
authors.lastname: Yu
authors.forename: An
authors.initials: A
authors.lastname: Xu
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D018957:CD59 Antigens / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002479:Inclusion Bodies; D008027:Light; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000032:analysis / Q000633:toxicity*; D010316:Particle Size; D013367:Submitochondrial Particles / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D001335:Vehicle Emissions / Q000032:analysis / Q000517:prevention & control / Q000633:toxicity*
chemical_list: D018957:CD59 Antigens; D009153:Mutagens; D001335:Vehicle Emissions; D000643:Ammonium Chloride; D003571:Cytochalasin B