NIH study finds low-dose nicotine does not promote tumor growth in mouse models of lung cancer:
Experiments in mice show that low levels of exposure to nicotine, equivalent to those in humans who use nicotine replacement therapy (NRT) to help them quit smoking, did not promote lung tumor growth. The study, by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, together with the results of another study published online Oct. 25, 2011, in Cancer Prevention Research, indicates that use of NRT for extended periods of time would be unlikely to cause an increase in lung cancer incidence rates of former smokers.
NRT was developed as an aid to tobacco cessation, the goal of which is to help reduce the incidence of the many serious health effects associated with smoking, such as heart disease and lung cancer. NRT has been shown to be effective and is approved by the U.S. Food and Drug Administration for use in the treatment of tobacco dependence. When used as directed, NRT can help increase a smoker’s chances of quitting smoking.
Although the levels of nicotine in NRT are substantially lower than what is delivered by cigarettes, a limited body of research—including some tissue culture studies conducted by NCI scientists—has suggested that even low levels of nicotine might promote tumor growth. Those earlier findings raised potential concerns about the safety of using NRT. The results of the current study in mice found no evidence to support this concern.
“This work actually contradicts some of our other preclinical studies that raised potential concerns about NRT safety,” said Phillip Dennis, M.D., Ph.D., of the Medical Oncology Branch in NCI’s Center for Cancer Research. “Our current findings may provide additional reassurance about the expanded use of NRT, which may be an important health benefit to people who are addicted to smoking and unable to quit using other recommended treatments.”
One of the study’s strengths is in its use of three separate mouse models of lung cancer to test nicotine at blood levels comparable to those in people who are using NRT to try to quit smoking. Two studies used a carcinogen-driven model in which mice of a certain strain called A/J are treated with a chemical that almost invariably causes mutations in the K-Ras gene in mice. K-ras mutations are common in tobacco-related lung cancers in humans. The chemical used in these experiments, called nicotine-derived nitrosamine ketone (NNK), is found in cured tobacco and is converted into a potent carcinogen by the body. The third study uses a transgenic mouse model (one that has DNA artificially inserted into it) that acquires mutations in K-Ras as the mice grow and develop.
In the carcinogen-driven models, mice that are susceptible to NNK-induced tumors were treated with NNK and given nicotine in their drinking water. The level of nicotine in the water was chosen to yield blood concentrations in the mice that are comparable to those in people who are using NRT. Lung tumors that developed in the mice were evaluated at different time points, and the concentration of a nicotine byproduct was measured in the blood. A similar approach was taken with the transgenic model, in which nicotine was placed in the drinking water for varying lengths of time, and tumors and nicotine byproduct levels were measured.
In all models, tumors were evaluated for any biochemical effects of nicotine, and none were observed. In fact, no matter the length of nicotine exposure, no adverse effects were seen on any tumor-related endpoints measured (tumor number, size, or metastasis) or on mouse survival.
“Our findings show that, when administered to mice to achieve levels similar to NRT users, nicotine has no effect on K-Ras-driven lung tumor development. Therefore, these studies may provide support to the expanded use of NRT to assist those who want to quit smoking,” said Dennis.
Dennis and his team caution that these are preclinical studies and that the models were defined by mutations in K-Ras, which may not be relevant to all smoking-related lung cancers.
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Reference: PA Dennis et al. Nicotine does not enhance tumorigenesis in mutant K-Ras-driven mouse models of lung cancer. Cancer Prevention Research, Oct. 25, 2011.