Why does asbestos cause lung cancer?

When we had some building working work done many years ago, there was a minor scare when one of the builders thought that a panel might be asbestos, thankfully turned out to be some reconstituted cement¬†chip product. But, if it had been asbestos it would have meant us evacuating our home, the recruitment of a licensed asbestos removal team, red alerts for the neighbours…all kinds of trouble.

So, what it asbestos and why is it such a worry in terms of health and in particular the ambulance-chasing lawyers’ favourite class action condition mesothelioma?

Asbestos (from the Greek meaning “unquenchable” or “inextinguishable” is not a single substance but rather six naturally occurring silicate minerals. The properties of asbestos made it a popular “fire-proof” material for manufacturers and builders as early as the late 19th century. When formed into sheets and blocks it also has good sound absorption, tensile strength, and electrical and chemical damage. When asbestos is used for its resistance to fire or heat, the fibres are usually mixed with cement or woven into fabric or mats. It has found use in construction, wiring, ovens, vehicle brakes and many other applications.

Unfortunately, it was discovered that breathing in tiny asbestos fibres causes serious health problems, including malignant lung cancer, mesothelioma and asbestosis (a type of pneumoconiosis). As such, the European Union banned all asbestos use and the extraction, manufacture and processing of asbestos products.

But, that still doesn’t answer the question as to what makes these silicate fibres so noxious.

Amosite and crocidolite are the two most hazardous forms of asbestos as they persist in the lungs for a long time causing chronic irritation. Mesothelioma has been observed in people occupationally exposed to chrysotile and even family members of those people who worked with asbestos. Asbestos exposure becomes a health concern when high concentrations of asbestos fibres are inhaled over a long time period.

Medicine net explains the problem quite succinctly; apparently size matters:

“Depending on their shape and size, asbestos fibers deposit in different areas of the lung. Fibers less than 3 mm easily move into the lung tissue and the lining surrounding the lung (pleura). Long fibers, greater than 5 mm, cannot be completely broken down by scavenger cells (macrophages) and remain in the lung tissue. These asbestos fibers can cause inflammation. Substances damaging to the lungs are then released by the cells of inflammation that are responding to the foreign asbestos material. The persistence of these long fibers in the lung tissue and the resulting inflammation seem to initiate the process of cancer formation.”

According to Liu et al in Chem Biol Interact recently, “Asbestos causes pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully elucidated.” They explain that accumulating evidence shows that alveolar epithelial cell (AEC) programmed cell death (apoptosis) is crucial in the response to noxious stimuli, including asbestos, but they have reviewed the literature on the role of asbestos in augmenting AEC apoptosis by the mitochondria- and p53-regulated death pathways that result from the production of iron-derived reactive oxygen species (ROS) and DNA damage. An additional review from DW Kamp also reviews current understanding.

It’s a complicated picture. Whereas hand-waving explanations involving the fibres causing inflammation and the notion of sub-microscopic threads of silicate intercalating themselves into the grooves of the DNA double helix, might help pad out the lay picture of asbestos’ health effects, there seems to be much work still needed to answer this post’s question.

That said, another clue was published in PNAS recently in which Haining Yang and Michele Carbone at the University of Hawai’i Cancer Research Center working with teams elsewhere in teh US and Europe seemingly addressed the paradox as to how asbestos fibres, which kill cells, could cause cancer, since a dead cell should not be able to grow and form a tumour. That team suggested that a process of ¬†“programmed cell necrosis” is initiated by the cell death, which releases high-mobility group box 1 protein (HMGB1), which in turn triggers a very specific inflammatory reaction, which releases mutagens and tumour-promoting factors. HMGB1 could thus represent a target for treating mesothelioma.

Research Blogging IconLiu, G., Beri, R., Mueller, A., & Kamp, D. (2010). Molecular mechanisms of asbestos-induced lung epithelial cell apoptosis Chemico-Biological Interactions, 188 (2), 309-318 DOI: 10.1016/j.cbi.2010.03.047