In today's headlines, we have seen that diesel truck drivers are more likely to develop lung cancer than other workers, according to researchers who examined the records of more than 31, 000 workers. Those researchers concluded that fresh, newly released diesel particles have a greater potential to cause DNA mutations that lead to lung cancer. California's Air Resources Board is due to consider the study's findings when it meets Friday to vote on a landmark regulation to reduce risk to the general public from 1 million diesel trucks in the state. This could be a harbinger for more environmental legislation to come -- and more attention to the science behind the findings.
Wolfgang Liedtke, M.D., Ph.D., and colleagues at Duke University, U.S. Environmental Protection Agency and Dartmouth-Hitchcock Medical Center have just published evidence of exactly how diesel particles interact with human airway cells to pave the way for cancerous growth, in an in-press, online version of Environmental Health Perspectives.
Their findings:
About 3/4 of the world's population holds the "bad set of cards" – they are susceptible genetically to one particular aspect of damage evoked by inhalation of diesel particles.
Diesel particles carry molecules that stimulate a pathway, the RAS "switch" that enhances cell growth and formation of cancers. RAS in turn switches on the production of collagenase by cells that cover human airways. Collagenase (MMP-1) is known to enhance spreading of airway cells that have just turned cancerous, also to enhance the development of chronic-obstructive pulmonary disease (COPD) and of emphysema, a lethal lung disease in which functional lung tissue is progressively lost. Production of collagenase by human cells comes in two flavors, a more "pedestrian" version vs. a "turbo-charged" version.
Jinju Li et al. from the labs of Drs. Sidney Simon and Wolfgang Liedtke at Duke University Medical Center showed that the "turbo-charged" version of the human collagenase gene (MMP-1 gene) is critical for the airway cell to produce vastly increased amounts of collagenase in response to diesel particles. It is known that approximately 3/4 of all humans, irrespective of sex or ethnicity, have at least one copy of the "turbo-charged" MMP-1 gene.
In addition, they were able to show that production of collagenase by the human airway epithelia is strictly dependent on beta-arrestin scaffolding molecules, discovered by Duke researcher Dr. Robert Lefkowitz more than 15 years ago. These findings indicate a susceptibility among a majority of all humans to suffer increased airway damage – including bronchial cancer as well as "non-malignant" chronic respiratory diseases – when inhaling diesel particles. Regarding the development of therapies for COPD and emphysema, the concept possibly would be an inhalant, for topical inhibition of critical switches in bronchial epithelial cells, such as inhibitors of RAS, beta-arrestins or collagenase.
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