Mesothelioma and Other Cancers Caused by Asbestos Through DNA Damage

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Exposure to crocidolite asbestos triggers enhanced DNA damage that can turn cells cancerous, according to a study published online September 25 in the American Journal of Respiratory Cell and Molecular Biology. The discovery might one day lead to a new method of screening people who have been exposed to asbestos and are at risk for mesothelioma and other cancers.

The connection between asbestos and cancers such as mesothelioma has been well documented. Because decades can pass before asbestos-related cancers are diagnosed, and patients with mesothelioma survive an average of just a few years, it is crucial to identify signs of increased cancer risk as early as possible. One way might be to look for DNA damage in patients who have been exposed to asbestos.

Crocidolite asbestos is thought to be the most dangerous form of this fibrous mineral. It leads to the creation of harmful molecules called reactive oxygen species (ROS) and triggers DNA damage that can cause normal cells to turn cancerous. The body tries to repair that damage, but it isn’t always successful.  This can lead to the creation of cancer like mesothelioma.

DNA is made up of a two-stranded double helix. When only one of those two strands is defective (called a single strand break), the other strand can be used as a template to repair the broken strand. When both strands are broken (called a double strand break), the body has more trouble fixing the damage. “As a result of not being repaired, the DNA can give rise to mutations,” says study author Val Vallyathan, PhD, Team Leader in Pathology and Physiology Research at the National Institute for Occupational Safety and Health, and Professor of Pathology at West Virginia University. Those mutations can lead to mesothelioma and other cancers.

Dr. Vallyathan and his colleagues looked at the ability of three substances—crocidolite asbestos, silica, and titanium dioxide—to trigger DNA damage in cells, and the genetic ability to repair that damage. Asbestos has already been proven to cause mesothelioma and lung cancer. Dr. Vallyathan included silica and titanium dioxide in the study because their cancer-causing potential is still widely debated.

“Silica is not fully confirmed as a carcinogen in humans, although several studies have shown that it is,” he says. “Titanium dioxide had been considered a very inert particle and had been used as a negative control in animal studies and cellular studies, but in recent years it has been shown that it is probably more toxic than what it was thought to be.”

The researchers exposed normal airway cells and lung cancer cells to all three substances. Although crocidolite asbestos, silica, and titanium dioxide all triggered DNA damage, asbestos was by far the most toxic to cells. It produced the highest amount of ROS production, and led to more DNA double strand breaks than either silica or titanium dioxide.

Asbestos caused continuous DNA damage in both the normal and cancerous cells, which the cells were unable to repair. That second hit of damage to already cancerous cells indicates that asbestos could trigger additional changes inside those cells, leading to more aggressive cancers like mesothelioma that are more likely to spread, Dr. Vallyathan says.

The authors say detection of DNA double strand breaks could be used to measure potential cancer risk in people who have been exposed to crocidolite asbestos. Dr. Vallyathan says that in future research, he would like to monitor the blood of people with known exposures to carcinogens such as asbestos, to determine whether DNA damage can be detected early.

Source: 
Msiska Z, Pacurari M, Mishra A, Leonard SS, Castranova V, Vallyathan V. DNA double strand breaks by asbestos, silica and titanium dioxide: possible biomarker of carcinogenic potential? Am J Respir Cell Mol Biol. 2009 Sep 25.

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