Particulate matter inhibits DNA repair and enhances mutagenesis

Exposure to ambient air pollution has been associated with adverse health effects including lung cancer. A recent epidemiology study has established that each 10 μg/m 3 elevation in long-term exposure to average PM 2.5 ambient concentration was associated with approximately 8% of lung cancer mortali...

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Bibliographic Details
Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2008-12, Vol.657 (2), p.116-121
Main Authors: Mehta, Manju, Chen, Lung-Chi, Gordon, Terry, Rom, William, Tang, Moon-shong
Format: Article
Language:English
Subjects:
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Host cell reactivation (HCR)
Medical sciences
Molecular and cellular biology
Molecular genetics
Mutagenesis
Mutagenesis. Repair
Nucleotide excision repair (NER)
Particulate matter
Toxicology
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Summary:Exposure to ambient air pollution has been associated with adverse health effects including lung cancer. A recent epidemiology study has established that each 10 μg/m 3 elevation in long-term exposure to average PM 2.5 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.
ISSN:1383-5718
1879-3592
DOI:10.1016/j.mrgentox.2008.08.015