National Institute of Health

Diesel Exhaust Can Damage the DNA in the Cells of Your Lungs

New evidence shows that particulate matter from diesel exhaust—a major air pollutant—can damage human lung fibroblast cells

The rising incidence of lung cancer worldwide has been linked to increasing levels of air pollutants, such as diesel exhaust particles. However, the biological events that occur in the body after exposure to these particles are poorly understood. A recent study by a group of scientists from Korea has now unearthed the smoking gun—DNA damage and genome-wide changes—which could flip the cancer switch in normal lung cells.

A new study examined how diesel exhaust particles, an important source of particulate matter and air pollutants, damage lungs at the genetic level

Photo courtesy: Shutterstock

Air pollution is a major cause for concern, especially in urban and densely populated areas. One key contributor to air pollution is fine particulate matter, such as diesel exhaust particles (DEP), which are generated due to the combustion of diesel. Owing to their small size, DEP can easily enter the respiratory tract, causing lung diseases like asthma, bronchitis, and even cancer.

The link between DEP and lung cancer in particular has become increasingly apparent in recent years. DEP are considered “carcinogens”—agents that cause cancer—and studies have demonstrated their toxicity against lung cells. However, these studies were based on animal cells or human cancer cells, limiting their generalizability to real-life conditions. Given the significance of understanding DEP-induced cancer development in healthy individuals, an assessment of how these particles affect normal human lung cells is warranted.

In their study published in Biomolecules, a research team led by Dr. Jung from the Korea National Institute of Health set out to address this gap. Owing to the major role of gene-level alterations in the development of lung cancer, the research team exposed normal human embryonic lung cells to DEP and then examined any gene-level changes using conventional assays. This study was supported by a fund (2019-NI-099-01, 2019-NI-098-01) by the Research of Korea Disease Control and Prevention Agency (KDCA).

Their preliminary experiments showed that exposure to DEP led to oxidative stress—a condition of imbalance in which volatile molecules produced by cells react with DNA, proteins, and other biomolecules and damage them—in lung cells. Subsequently, using a comet assay in which damaged DNA appears to form a comet tail-like structure, they observed the breakage of DNA strands in cells exposed to DEP. “Our results provide irrefutable evidence that DEP cause DNA strand breaks, which in turn result in chromosomal abnormalities and often represent the first step towards carcinogenesis,” state the researchers, adding that these breaks are often caused by oxidative stress.

To further understand any chromosomal instability caused by DEP, the research team performed microscopic examinations and observed that DEP exposure increased the number of micronuclei (small broken-off fragments of chromosomes) in lung cells, supplementing the evidence pointing to the genotoxic effects of DEP.

Next, to explore the genome-wide effects of DEP, the researchers examined whether exposure to DEP alters gene expression, a hallmark of cell behavior. Using a technique called “untargeted RNA-sequencing,” they found that lung cells exposed to DEP show the suppressed activity of genes required for normal DNA damage repair and cell division, which has been implicated in the development of cancer. “Our study is the first to use untargeted RNA-sequencing to understand how DEP can change the landscape of global gene expression in normal human lung WI-38 cells,” say the researchers. “Overall, our findings provide a comprehensive insight into the alterations DEP cause to chromosomes and gene regulation in lung cells, thereby causing cell damage and carcinogenesis. Although validation experiments will be required to strengthen them further, our results are of great significance from a clinical translation standpoint,” they add.

The findings of this study, which explain the link between fine particles like DEP and lung cancer, represent an important breakthrough in the journey towards the clinical management of the disease. “Lung cancer and air pollution are major public health problems in several countries, including Korea. Understanding why lung cells turn cancerous after being exposed to air pollutants could be instrumental in developing strategies for preventing and treating the associated diseases,”  says the research team, hopeful of the road ahead.

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About National Institute of Health in Korea 

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.

Website: http://www.nih.go.kr/eng/  

About Dr. Ji-Won Jung

Dr. Ji-Won Jung is the head of the Division of Research Planning, Korea National Institute of Health. He currently plays an important role in establishing and coordinating the research agenda for KNIH.