New studies suggest that overloading the body with iron may be another way asbestos can trigger mesothelioma. And ridding the body of that excess iron may eventually be another way to help manage this cancer.
Malignant mesothelioma is caused by exposure to asbestos, especially crocidolite and amosite asbestos, whose tiny sharp fibers contain high amounts of iron. In recent years, medical researchers have confirmed that chronic inflammation caused by the irritation of asbestos fibers appears to be one of the triggers for mesothelioma. But mounting evidence suggests that the iron in asbestos may also play a role in this aggressive cancer.
While iron is essential for health, numerous epidemiological studies have shown it to be carcinogenic in high amounts. To test the connection between iron and mesothelioma, scientists repeatedly injected iron saccharate into the peritoneal cavity of lab rats. As predicted, many of the rats developed peritoneal mesothelioma.
When these mesothelioma cells were analyzed using an array-based comparative genomic hybridization (aCGH) and gene expression test, they were found to have alterations in a part of the DNA responsible for tumor suppression. The genes, called CDKN2A/2B are responsible for triggering cell production of enzymes that normally help prevent cancer. They also found an overabundance of the glycoprotein uromodulin in the mesothelioma cells. These findings suggest that the presence of excess iron put the cells under oxidative stress.
Although the genomic alternations were evident in all types of mesothelioma cells studied, they were most pronounced in mesothelioma cells of the sarcomatoid type, the most deadly form of the cancer.
In a recent article on the iron-cancer connection, Japanese researcher Shinya Toyokuni wrote, “CDKN2A/2B are the second most frequently inactivated tumor suppressing genes in human cancers.” Toyokuni suggested that, “iron regulation may be the next target for human longevity.”
Toyokuni, S, “Mysterious link between iron overload and CDKN2A/2B”, January 2011, Journal of Clinical Biochemistry and Nutrition”, pp. 48-9.
Hu, Q et al, “Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma”, March 2010, Laboratory Investigation, pp. 360-373.