Epigenetic Changes Induced by Air Toxics: Formaldehyde Exposure Alters miRNA Expression Profiles in Human Lung Cells

By Rager, Julia E.; Smeester, Lisa et al. | Environmental Health Perspectives, April 2011 | Go to article overview

Epigenetic Changes Induced by Air Toxics: Formaldehyde Exposure Alters miRNA Expression Profiles in Human Lung Cells


Rager, Julia E., Smeester, Lisa, Jaspers, Ilona, Sexton, Kenneth G., Fry, Rebecca C., Environmental Health Perspectives


BACKGROUND: Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehyde-induced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key post-transcriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first study to examine perturbations in global miRNA levels resulting from formaldehyde exposure.

OBJECTIVES: We investigated whether cellular miRNA expression profiles are modified by formaldehyde exposure to test the hypothesis that formaldehyde exposure disrupts miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease.

METHODS: Human lung epithelial cells were grown at air-liquid interface and exposed to gaseous formaldehyde at 1 ppm for 4 hr. Small RNAs and protein were collected and analyzed for miRNA expression using microarray analysis and for interleukin (IL-8) protein levels by enzyme-linked immunosorbent assay (ELISA).

RESULTS: Gaseous formaldehyde exposure altered the miRNA expression profiles in human lung cells. Specifically, 89 miRNAs were significantly down-regulated in formaldehyde exposed samples versus controls. Functional and molecular network analysis of the predicted miRNA transcript targets revealed that formaldehyde exposure potentially alters signaling pathways associated with cancer, inflammatory response, and endocrine system regulation. IL-8 release increased in cells exposed to formaldehyde, and results were confirmed by real-time polymerase chain reaction.

CONCLUSIONS: Formaldehyde alters miRNA patterns that regulate gene expression, potentially leading to the initiation of a variety of diseases.

KEY WORDS: air pollution, environment, formaldehyde, gene regulation, human lung cells, miRNA, systems biology. Environ Health Perfect 119:494-500 (2011). doi:10.1289/ehp.1002614 [Online 9 December 2010]

Current indoor and outdoor air quality contributes significantly to global increases in morbidity and mortality (Brunekreef and Holgate 2002; Burnett et al. 2001; Smith and Mehta 2003). Epidemiological studies have shown char formaldehyde, a known air toxic, causes increased risk of childhood and adult asthma (Rumchev et al. 2002; Wieslander et al. 1997), acute respiratory tract illness (Turhill 1984), nasopharyngeal cancer (Vaughan et al. 2000), and possibly leukemia (Zhang et al. 2010a). In animal studies, strong links have been made between formaldehyde exposure and nasal carcinoma (Kerns et al. 1983). Furthermore, the International Agency for Research on Cancer (IARC) has classified formaldehyde as a known human carcinogen (IARC 2006).

In outdoor environments, formaldehyde is present due to direct emissions from anthropogenic and biogenic sources, and it is also formed as a secondary chemical product through hydrocarbon atmospheric chemistry [World Health Organization (WHO) 2001]. Anthropogenic sources of formaldehyde include automobile exhaust, power plants, manufacturing facilities, and incinerators (U.S. Environmental Protection Agency 2007; WHO 2001). Ambient air has been estimated to contain formaldehyde at levels between 0.0008 and 0.02 ppm (WHO 2001). Higher formaldehyde exposure occurs within indoor environments, where humans inhale levels estimated between 0.02 and 0.3 ppm, depending on the presence of tobacco smoke (WHO 2001). The highest formaldehyde levels are found in certain occupational environments, such as industries related to resin, plastics, wood, paper, insulation, textile, and chemical productions, as well as medical institutions using disinfectants and embalming products. In these high-exposure cases, occupational workers are exposed to, on average, approximately 0. …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

Epigenetic Changes Induced by Air Toxics: Formaldehyde Exposure Alters miRNA Expression Profiles in Human Lung Cells
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen
Items saved from this article
  • Highlights & Notes
  • Citations
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Search by... Author
    Show... All Results Primary Sources Peer-reviewed

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.