title: Particulate matter inhibits DNA repair and enhances mutagenesis.
abstract: Exposure to ambient air pollution has been associated with adverse health effects including lung cancer. A recent epidemiology study has established that each 10 microg/m3 elevation in long-term exposure to average PM2.5 ambient concentration was associated with approximately 8% of lung cancer mortality. The underlying mechanisms of how PM contributes to lung carcinogenesis, however, remain to be elucidated. We have recently found that transition metals such as nickel and chromium and oxidative stress induced lipid peroxidation metabolites such as aldehydes can greatly inhibit nucleotide excision repair (NER) and enhance carcinogen-induced mutations. Because PM is rich in metal and aldehyde content and can induce oxidative stress, we tested the effect of PM on DNA repair capacity in cultured human lung cells using in vitro DNA repair synthesis and host cell reactivation assays. We found that PM greatly inhibits NER for ultraviolet (UV) light and benzo(a)pyrene diol epoxide (BPDE) induced DNA damage in human lung cells. We further demonstrated that PM exposure can significantly increase both spontaneous and UV-induced mutagenesis. These results together suggest that the carcinogenicity of PM may act through its combined effect on suppression of DNA repair and enhancement of DNA replication errors.
authors.affiliation: Departments of Environmental Medicine, Pathology and Medicine, New York University School of Medicine, Tuxedo, New York 10987, United States.
authors.forename: Manju
authors.initials: M
authors.lastname: Mehta
authors.forename: Lung-Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Terry
authors.initials: T
authors.lastname: Gordon
authors.forename: William
authors.initials: W
authors.lastname: Rom
authors.forename: Moon-Shong
authors.initials: MS
authors.lastname: Tang
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000393:Air Pollutants / Q000633:toxicity*; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D016296:Mutagenesis; D052638:Particulate Matter / Q000633:toxicity*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide