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Citation
Tags
HERO ID
1010792
Reference Type
Journal Article
Title
Classification of polycyclic aromatic hydrocarbons based on mutagenicity in lung tissue through DNA microarray
Author(s)
Hirano, M; Tanaka, S; Asami, O
Year
2013
Is Peer Reviewed?
Yes
Journal
Environmental Toxicology
ISSN:
1520-4081
EISSN:
1522-7278
Volume
28
Issue
11
Page Numbers
652-659
Language
English
PMID
21887816
DOI
10.1002/tox.20761
Web of Science Id
WOS:000326276900006
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced in the combustion of organic matter. Exposure to PAHs raises the risk of lung cancer and inflammatory and allergic disorders such as asthma. DNA microarray technologies have been applied to research on toxicogenomics in the recent years. To evaluate the mutagenicity of PAHs and constituents of environmental pollutants in lung tissue, including metabolic activation, human alveolar epithelial type II cells (A549) were treated with nonmutagenic PAH pyrene and with the mutagenic PAHs benzo-[a]-pyrene, 1-nitropyrene, or 1,8-dinitropyrene. Comparison of genome-wide microarray expression profiles between a nonmutagenic and a mutagenic PAH-treated group revealed that xenobiotic response genes such as CYP1B1 were commonly upregulated in two groups and that DNA damage induced genes, especially p53-downstream genes such as p21 (CDKN1A) were upregulated only in the mutagenic PAH-treated group. Pretreatment with cytochrome P450 inhibitor α-naphthoflavone or p53 inhibitor pifithrin-α inhibited the benzo-[a]-pyrene-induced p21 expression. These data suggest that when PAHs enter the cells, lung epithelium induces PAH metabolic activating enzymes, and then the DNA damages-recognition signal is converged with p53 downstream genes. This metabolic activation and DNA damage is induced in lung epithelium, and the mutagenicity of PAHs can be classified by DNA microarray expression profiles. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.
Keywords
Cancer; Cytochrome P450; DNA damage; DNA microarray; Lung; Metabolic activation; Mutagenicity; P53; PAH; Polycyclic aromatic hydrocarbon
Tags
IRIS
•
Benzo(a)pyrene (BaP)
Considered
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