SACRAMENTO, Calif. - The aroma of burning tobacco wafts gently out of Hanspeter Witschi's small laboratory at UC Davis. It's entirely out of place at an institution where all smoking is banned, but mice, not people, inhabit this little corner of Marlboro Country.

Witschi, associate director of the Institute for Toxicology and Environmental Health, has been studying the effects of secondhand smoke on mice for almost 10 years. What he's learned may have important implications for humans. In research published in the journal Carcinogenesis, Witschi, Dale Uyeminami, Dexter Moran and Imelda Espiritu, all of UC Davis, found that a diet of dexamethasone and myoinositol significantly reduced the incidence of lung cancer in male mice exposed to heavy cigarette smoke. Dexamethasone is a corticosteroid used to treat asthma while myoinositol is a constituent of cereal bran.

It is, Witschi believes, the first animal model study to test substances that might prevent smoking-induced lung cancer.

"We tested several compounds that had previously been shown to prevent cancer, but these studies were done on mice injected with tobacco carcinogens," Witschi explained. "We tested these same compounds on mice who had inhaled whole cigarette smoke, a model that is much more comparable to how humans develop lung cancer." Getting mice to inhale smoke in a manner that is both effective and humane is no easy task. As Witschi notes wryly, "Mice are too smart to smoke. In early experiments, scientists blew smoke directly into their faces, but the animals would hold their breath."

Witschi uses a smoke inhalation machine designed in 1994 by Steven Teague and Kent Pinkerton of UC Davis and Roger Jenkins of the Oak Ridge National Laboratory. The device loads 10 cigarettes at a time into a chambered wheel attached to a machine that smokes more than two cartons of cigarettes a day. With each turn of the wheel, 10 whispery puffs of smoke escape.

Researchers use unlabeled research cigarettes from the Tobacco Research Institute in Lexington, Kentucky, with no additives or flavoring agents to skew their findings.

The smoke generated by the machine is directed into the otherwise clean and well-ventilated cages of a breed of mice with a genetic susceptibility for developing tumors. In his Toxic Pollutants Health Research lab, mice are exposed to cigarette smoke for six hours a day, five days a week - "roughly the way workers in industry would encounter secondhand smoke," according to Witschi.

A medical doctor and professor of toxicology, Witschi does research on acute and chronic pulmonary disease caused by environmental pollutants. After establishing a connection between secondhand smoke and lung tumors in mice, he set out to test the potential of several anti cancer compounds.

Humans are the only animals who smoke, for which they pay a fearsome price. More than 400,000 Americans die annually from smoking-related causes, including 150,0000 from lung cancer. More than 90 percent of all people diagnosed with lung cancer are current or former smokers. Average survival time after a lung cancer diagnosis is less than a year.

In research funded by the National Institute of Environmental Health Sciences, Witschi fed experimental mice diets of special compounds thought to prevent lung cancer. This included limonene, a phytonutrient found in citrus peels; a selenium compound; aspirin, green tea and two kinds of isothiocynates (an antioxidant nutrient found in cabbage).

The mice were exposed to cigarette smoke for five months, then placed in clean air for four more months to mimic what happens to people who smoke and then quit. Based on previous studies, researchers would expect 89 percent of the mice to develop lung tumors, with an average of 2.4 tumors per animal. None of the other compounds made a dent in this statistic. But mice who got a combination of dexamethasone and myoinositol saw tumor incidence drop to 62 percent and to one tumor per animal.

The dexamethasone-myoinositol regimen also worked for mice who were exposed to smoke first and then given the special diet.

"Our observation that dexamethasone and myoinositol were highly effective in preventing lung cancer in mice who had 'quit' smoking may be of practical significance," Witschi said. "Chemoprevention administered to people who have quit smoking might reduce their risk of developing the disease."

That's encouraging news for the estimated 40 million Americans who have kicked the nicotine habit, and the thousands more who will quit this year.

"We've had a lot of disappointments in the field of chemoprevention for lung cancer," said Witschi. "In the late 1970s they thought beta carotene reduced the risk of lung cancer in smokers, but when they tested it further, they found it actually increased the risk of lung cancer."

Witschi hopes his model will be useful in preclinical testing of chemoprevention treatments before they are given to humans.

In the meantime, he continues to test other possible chemoprevention compounds in hopes of clarifying the link between lung cancer in mice and in humans.

Editor: An abstract of Dr. Witschi's article in Carcinogenesis is available at http://carcin.oupjournals.org/

To receive a copy of the article call Laurie Slothower at (916) 734-9023.

Copies of all news releases from UC Davis Health System are available on the web at http://news.ucdmc.ucdavis.edu.

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(NC)-Lung cancer, the most preventative of all human cancers, remains the leading cause of cancer death for both men and women. Several studies have shown that vitamin E supplementation is associated with a lower risk of developing lung cancer in non-smokers. Unfortunately, the same benefit was not seen in smokers. The most effective health action for smokers is still to stop smoking.

It is believed that the beneficial effect of vitamin E is a consequence of its antioxidant role, which may be enhanced when taken in combination with other antioxidants such as vitamin C, beta-carotene and selenium. All of these nutrients are available in a quality multivitamin such as Centrum®, available in your local pharmacy. For more information on supplementation, visit www.centrumvitamins.ca.

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