Thursday, July 4, 2013

Cancer-Promoting Mechanisms of Overlooked Components in Secondhand Smoke


Tobacco smoke, diesel exhaust and oil combustion carry polycyclic aromatic hydrocarbons -- PAHs that are known to cause cancer.

But of these PAHs, the obviously dangerous high-molecular-weight PAHs like benzo[a]pyrene (BaP) have received the vast majority of research attention. Their low-molecular-weight cousins have been largely overlooked, in part because studies have shown that these compounds alone aren't very successful at mutating genes in cancer-causing ways.

A University of Colorado Cancer Center study explores two of these low-molecular-weight (LMW) PAHs -- 1-methylanthracene (1-MeA) and 2-methylanthracene (2-MeA) -- and shows that while they don't necessarily cause cancer, 1-MeA promotes conditions that will likely allow cancer to grow.

There's a big distinction between initiating cancer and promoting it,
says Asst Prof Alison Bauer, CU Cancer Center investigator.

Her study showed that in a mouse cell model using a progenitor cell of lung cancer, the LMW 1-MeA promoted inflammation and increased mitogenic pathways, both of which are linked to tumor promotion. 2-MeA, while nearly structurally identical, did not.

Among other effects, Bauer and colleagues found that 1-MeA disrupts communication between cells, affecting the "gap junctions" across which adjoining cells pass information. 1-MeA also upregulates the gene COX2, which has been shown in other studies to create an over-aggressive inflammatory response -- and this inflammation in turn can promote tumor growth.

There are many different PAHs in secondhand smoke
Bauer says. "Some are obviously dangerous like BaP, which directly mutates genes. Others, like 1-MeA, we known very little about. Think about all these PAHs like chess pieces -- first you have to know how each piece moves and then you can start looking at how they all work together."

"With smoking rates decreasing, we think this problem is going away, but high levels of secondhand smoke still exist in the U.S., for example in some apartment buildings," Bauer says. "And around the world, in China, Russia, Poland and many other countries, secondhand smoke is still a major issue. Knowing the effects of these LMW PAHs like 1-MeA could help us prevent or treat cancers associated with them."


The above story is based on the June 25, 2013 news release reprinted from materials provided by University of Colorado Denver.

The study has been published in the journal PLoSOne:                                                                
Osgood RS, Upham BL, Hill T, Helms KL, Velmurugan K, Babica P, Bauer AK. Polycyclic Aromatic Hydrocarbon-Induced Signaling Events Relevant to Inflammation and Tumorigenesis in Lung Cells Are Dependent on Molecular Structure. PLoS ONE, 2013; 8 (6): e65150 DOI: 10.1371/journal.pone.0065150

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