MEMORANDUM FOR: Science Writers and Editors on the Journal Press List

July 15, 1999 (EMBARGOED FOR RELEASE 4 P.M. EDT July 20)

Julianne Chappell, Executive Editor, Dan Eckstein, (301) 986-1891, ext. 119

Reducing Smoking-Related Lung Cancers

The complexity of tobacco smoke makes it difficult to understand every aspect of its role in lung cancer, but concentrating on known carcinogens in the smoke simplifies the problem and may point the way to new approaches for preventing lung cancer.

This is one of the central points presented by Stephen S. Hecht, Ph.D., University of Minnesota Cancer Center, in a review paper in the July 21 issue of the Journal of the National Cancer Institute.

Lung cancer is the leading cause of cancer death in both men and women in the United States, with more than 158,900 deaths expected in 1999. Smoking causes 90% of the male and 75%-80% of the female deaths due to lung cancer. There are one billion smokers worldwide, and about 500 billion cigarettes were sold in the United States in 1995. Although there has been some decrease in the number of smokers in this country as a result of various antismoking campaigns, the goal of a smoke-free society is still distant.

The smoke emerging from a cigarette mouthpiece contains about 1010 particles per mL; these particles contain at least 3500 compounds and most of the carcinogens. Of the 55 carcinogens identified in cigarette smoke, 20 convincingly cause lung cancer in laboratory animals or humans, and a great deal is known about the mechanisms by which these compounds cause lung cancer.

The author presents a chart that traces the smoking-cancer pathway: Nicotine addiction causes persistent cigarette smoking; smoking introduces carcinogens into the lungs; some of the carcinogens are detoxified and excreted, while others combine with DNA to form adducts; some of these adducts are repaired, while others lead to either cell death (apoptosis) or persistent genetic mutations that can result in lung cancer. Fewer than 20% of smokers will progress along this pathway fully to develop lung cancer. The author notes that it is important to clarify those factors that determine which smokers are susceptible to lung cancer and to find natural protective mechanisms.

An important approach to reducing the incidence of lung cancers in addicted smokers and ex-smokers is chemoprevention. Many agents that can block carcinogen activation or enhance detoxification are known, and the further development of effective chemopreventive agents should be a major priority for reducing the number of smoking-related lung cancers.

Contact: Teri Charest, University of Minnesota, Minneapolis (612) 624-4604; fax (612) 625-2129.

Vitamins C and E Can Reduce Hormone-Induced Cancer-Related Actions in Prostate Cancer Cells

Laboratory studies of prostate cancer cells show that vitamins C and E can counteract the negative effects associated with male hormones, effects that are linked to the development of prostate cancer.

In a report appearing in the July 21 issue of the Journal of the National Cancer Institute, Maureen Ripple, Ph.D., George Wilding, M.D., and colleagues at the University of Wisconsin, present the results of their studies involving two prostate cancer cell lines.

The authors used LNCaP cells, which are responsive to male hormones, and DU145 cells, which are hormone independent. To growing cultures of these cells they added low concentrations of male hormone (specifically, R1881, a synthetic androgen) and 0, 25, 50, 100, or 500 µM each of vitamins C and E. After various growth times, they harvested the cells and analyzed for reactive oxygen species and for the DNA binding of transcriptional activators AP-1 and NF-{kappa}B. AP-1 and NF-{kappa}B are protein complexes that mediate cellular response to various external signals by binding to distinct DNA sites. Male hormones influence the intracellular oxidation state in cultured cells. Since AP-1 and NF-{kappa}B are sensitive to the oxidation state, the authors determined if hormones stimulate the binding activity and if the antioxidants vitamin C and E influence the effect.

The DU145 cells were not affected by the addition of male hormones, while the LNCaP cells, after 96 hours of exposure to R1881, had reactive oxygen species (ROS) levels 86% higher than in untreated control cells. A much smaller increase in ROS was seen in those cells treated with both R1881 and vitamins C and E. This finding is important in that ROS are believed to play important roles in tumor development.

Hormone treatment alone increased AP-1 and NF-{kappa}B binding activity in the LNCaP cells but not in the androgen-independent DU145 cells. Again, addition of vitamins C and E to the hormone solution clearly decreased the amount of DNA binding of both the AP-1 and NF-{kappa}B complexes. However, the timing and concentrations of vitamins needed to produce an effect on AP-1 and NF-{kappa}B binding were different, suggesting that the ROS involved in androgen-induced AP-1 and NF-{kappa}B regulation are different. The authors conclude that understanding how antioxidants, such as vitamins C and E, act to reduce cancer risk will aid in developing cancer prevention strategies.

Contact: Michael Felber, University of Wisconsin, Madison, (608) 265-7427; fax (608) 263-6394.

Note: This memo to reporters is from the Journal staff and is not an official release of the National Cancer Institute (NCI) or Oxford University Press (OUP) nor does it reflect NCI or OUP policy. In addition, unless otherwise stated, all articles and items published in the Journal reflect the individual views of the authors and not necessarily the official points of view held by NCI, any other component of the U.S. government, OUP, or the organizations with which the authors are affiliated. Neither NCI nor any other component of the U.S. government nor OUP assumes any responsibility for the completeness of the articles or other items or the accuracy of the conclusions reached therein.



             
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