Cigarettes are addictive, and smoking them causes lung cancer. Of the two "active ingredients" listed on the packs, scientists had initially assumed that nicotine was the addictive agent, and tar the carcinogen. Recent evidence, however, suggests that things are not that simple, and that nicotine and its derivatives themselves might also promote cancer development and progression. Phillip Dennis and colleagues at the US National Cancer Institute in Bethesda, have studied the effect of nicotine and the nicotine-derived nitrosamine NKK on normal lung epithelial cells--i.e. those cells that are exposed to inhaled smoke and in which lung cancer starts.

As they report in the January 2nd issue of the Journal of Clinical Investigation, stimulation of lung epithelial cells with amounts of nicotine and NKK equivalent to those seen in smokers, resulted in the activation of a molecular pathway -- the so-called Akt pathway -- that promotes cell growth and survival. They also found that the Akt pathway was active in the lungs of mice treated with NKK and in lung cancer tissue from smokers.

This is significant because programmed cell death, or apoptosis, is one of the body's most effective defense mechanisms against cancer. Cells are constantly checking their "normal status", and are poised to commit suicide at the first sign of irregularities, thus protecting the host from propagation of abnormal cells that can, over time, form tumors. Virtually all cancers have found ways to undermine this defense mechanism, and activation of the Akt survival pathway is one of them.

The article is accompanied by a Commentary from John Minna, Director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center in Dallas, who discusses the findings in the context of other recent results that also suggest that nicotine and its deri
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Contact: Brooke Grindlinger Ph.D.
science_editor@the-jci.org
212-342 -9006
Journal of Clinical Investigation
2-Jan-2003