New research from Japan suggests that removing some blood from the body might offer a way to delay the development of mesothelioma in people exposed to asbestos.
Nearly all cases of malignant mesothelioma occur in people with a history of asbestos exposure. Scientists know that asbestos causes mesothelioma. But they still do not know exactly how.
What is clear is that both iron and byproducts of metabolism called reactive oxygen species (ROS) appear to play a role. Blood removal or phlebotomy can temporarily reduce iron and ROS levels.
The new report from Yasumasa Okazaki, a pathologist with Japan’s Nagoya University Graduate School of Medicine, details how phlebotomy in asbestos-exposed mice delayed the development of mesothelioma. It offers hope that this approach might one-day work for people, too.
Asbestos and the Development of Mesothelioma
The exact mechanism by which asbestos fibers cause the development of mesothelioma in some people is not fully understood. What researchers do know for sure is that the process is multifactorial.
One of those factors is inflammation. Inflammation comes from shards of asbestos which lodge in the tissue after they are inhaled or swallowed and stay there indefinitely. In some cases, chronic inflammation at the cellular level can alter the cells and trigger mesothelioma.
Another factor is iron. Even though people need a certain amount of iron to be healthy, past studies show that people and laboratory animals with mesothelioma have an overload of iron in their systems. This suggests that iron has an impact on mesothelioma carcinogenesis.
A third potential cause for the development of mesothelioma is oxidative stress. This is an imbalance between the production of free radicals (like ROS) and the body’s ability to counter their toxicity with antioxidants.
Releasing Iron and ROS Delays Mesothelioma Onset in Lab Animals
It takes an average of 30 to 40 years for mesothelioma symptoms to show up after asbestos exposure. During that time, the bodies of asbestos-exposed people are like ticking time bombs. There is nothing doctors can do to keep patients from eventually developing mesothelioma.
Scientists at Nagoya University used rats and mice to try to understand the molecular mechanisms behind the development of mesothelioma so they could find ways to prevent it.
One experiment involved rats with sarcomatoid mesothelioma. Sarcomatoid mesothelioma is a very aggressive subtype of mesothelioma. When researchers gave the rats a drug that reduced the amount of iron in their bodies, it reduced the rate of high-grade disease.
In another experiment, they removed blood from mice with asbestos-induced mesothelioma. They report that phlebotomy delayed the development of mesothelioma in the mice.
A third experiment used mice that had been genetically altered to produce lower amounts of ROS. These mice developed mesothelioma much more slowly than would normally be expected.
“These results indicate the importance of iron and ROS in mesothelial carcinogenesis,” concludes Dr. Okazaki. The article appears in the most recent issue of Pathology International.
Okazaki, Y, “Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species”, December 29, 2021, Pathology International, https://onlinelibrary.wiley.com/doi/10.1111/pin.13196
Li, J, et al, “Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis”, April 18 2016, Cancer Science, https://onlinelibrary.wiley.com/doi/full/10.1111/cas.12947