26 Apr 2000: Cancer-Protective Regimen Demonstrated, for First Time, to Prevent Tobacco Smoke-Related Lung Tumors -- in Mice

Four scientists said today that a "chemoprevention" regimen has been demonstrated, for the first time, to be highly effective in preventing lung tumors in male mice exposed to five months of heavy tobacco smoke. The regimen not only worked when given daily while the mice were exposed but when begun later, after the mice had been returned to clean air.

The scientists said they hoped their findings would lead to measures to prevent lung cancers in humans. Most lung cancer is associated with smoking -- and the rate peaks in men and women who have just quit.

The researchers -- Hanspeter Witschi, Dale Uyeminami, Dexter Moran and Imelda Espiritu, all of the University of California-Davis (http://www.ucdavis.edu/) - reported their work in the journal Carcinogenesis (http://carcin.oxfordjournals.org/) today. They said that a diet regimen containing myoinositol and dexamethasone proved successful in protecting mice exposed to cigarette smoke.

Myoinositol is derived from cereal brans. Dexamethasone is a corticosteroid drug.

The regimen and several that did not prove successful were tested under a grant from the National Institute of Environmental Health Sciences (http://www.niehs.nih.gov), one of the institutes of the National Institutes of Health (http://www.nih.gov) . The combination regimen worked in mice when it was given during the five months of exposure to tobacco smoke -- or in the weeks afterward, Dr. Witschi said. The air the mice breathed was heavily contaminated with tobacco smoke to simulate smoking, "which mice are too smart to do," he said. Then, they spent four months in clean air to simulate quitting.

Dr. Witschi (http://www.envtox.ucdavis.edu/CEHS/faculty/Witschi.htm) said that this work provides the first "animal model" for testing agents that might protect against smoking-induced lung cancer. He said he hopes the model will be useful in preclinical testing of possible preventive therapies before they are given to human subjects. The four scientists also tested - without success - a half dozen other regimens that seemed promising. All had previously been shown to prevent various cancers in experimental animals, but none, Dr. Witschi believes, had been tested against smoke-induced lung tumors.

Ironically, not only do about a quarter of the population risk lung cancer by continuing to smoke, recent quitters may remain for some time at increased risk - probably, many experts think, because a number of them quit because of chronic cough or other conditions that preceded a diagnosis of lung cancer. "Chemoprevention agents" might be added to current smoking cessation kits to reduce lung cancer risk, Dr. Witschi speculated.

He emphasized, however, that there is no indication that the agents would protect against other diseases associated with smoking.

The animals kept for five months in smoke had a lung tumor incidence of 89 percent, and an average of 2.4 tumors per animal, but these figures dropped to 62 percent and 1. tumor per animal in those who then got the myoinositol-dexamethasone therapy. These lower rates were very nearly identical to the rates of animals never exposed to smoke.

The other test substances, including green tea, also had been shown to prevent lung and other cancers caused by one or more chemicals in tobacco smoke. But they did not protect against the cancer-causing effects of whole tobacco smoke in these tests.

The smoke was produced using standard cigarettes purchased from the Tobacco & Health Research Institute (http://www.uky.edu/KTRDC/) at the University of Kentucky (http://www.uky.edu/) , Lexington.

Dr.Witschi is available at (530)752-0915 or e-mail hrwitschi@ucdavis.edu.