Carcinogenic Effect of Asbestos Linked to Chronic Inflammation

Cancer researchers have identified the molecular basis for how a potent cytotoxic agent like asbestos is able to function as a carcinogen.

Exposure to asbestos is associated with the risk of developing mesothelioma, a malignant cancer of the membranes that cover the lungs and abdomen and is resistant to current therapies. Since asbestos kills human mesothelial cells (HM), it has been difficult to understand how this substance could also act to trigger mesothelioma formation.

Now, a study published in June 28, 2010, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) has presented an explanation for this paradox by linking asbestos-induced HM cell death, which is a regulated form of necrosis, to carcinogenesis.

Asbestos-exposed HM cells activate the enzyme poly(ADP-ribose) polymerase, secrete hydrogen peroxide, deplete ATP, and translocate high-mobility group box 1 protein (HMGB1) from the nucleus to the cytoplasm, and into the extracellular space. The release of HMGB1 induces macrophages to secrete TNF-alpha (tumor necrosis factor-alpha), which protects HM from asbestos-induced cell death and triggers a chronic inflammatory response. Protection from cell death in an environment of chronic inflammation favors transformation of HM into cancer cells.

This study emphasized the role of inflammation in the development of mestothelioma and suggested novel clinical tools to identify exposed individuals and prevent or decrease tumor growth. The investigators at the Cancer Research Center of Hawaii (Honolulu, USA) ponder whether it is possible to prevent mesothelioma, like colon cancer, simply by taking aspirin or similar drugs that stop inflammation. This hypothesis will be tested in future studies.

Related Links:
Cancer Research Center of Hawaii