Chapter 23 Protection
Against
Nitrosamine-Induced by
Green
Tobacco-Specific, Lnng
T e a a n d Its 1
1,2
Tumorigenesis Components 3
1
Fung-Lung Chung , Yong Xu , Chi-TangHo ,Dhimant Desai , and Chi Han 2
Downloaded by CORNELL UNIV on July 31, 2016 | http://pubs.acs.org Publication Date: October 1, 1992 | doi: 10.1021/bk-1992-0507.ch023
1
Division of Chemical Carcinogenesis, American Health Foundation, One Dana Road, Valhalla, NY 10595 Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Nan Wei Road 29, Beijing 100050, People's Republic of China Department of Food Science, Rutgers, The State University of New Jersey, P.O. Box 231, New Brunswick, NJ 08903 2
3
The effects of Chinese green tea, (-)-epigallocatechin gallate (EGCG) and caffeine on 4-(methylnitrosamino)l-(3-pyridyl)-l-butanone (NNK) induced lung tumorigenesis in A/J mice were studied. Mice were given 2% tea infusion as drinking water, 560 ppm EGCG or 1120 ppm caffeine in water for 13 weeks. Two weeks later, NNK (11.65 mg/kg b.w.) was administered by gavage 3 times weekly for 10 weeks. The bioassay was terminated 6 weeks after the last NNK gavage. All mice treated with NNK only developed lung adenomas with a multiplicity of 22.5 tumors per mouse. NNK treated mice that drank tea or water containing EGCG developed only 12.2 and 16.1 tumors per mouse, respectively. This corresponds to a 45% and 30% reduction in lung tumor multiplicity. Little difference in water and dietary consumption was found among all the groups. However, mice that drank tea or caffeine solution showed consistently lower body weight gains than mice given water of EGCG solution. We also observed small but significant reduction of lung tumor multiplicity in the mice that were treated with caffeine solution. These results suggest that green teas can inhibit NNK -inducedlung tumors in mice and that the effect appears primarily due to its major polyphenol, EGCG. Cigarette smoking is a major cause of cancer in developed countries. It is estimated that 25-40% of all cancers in the U.S. can be attributed to tobacco use (1). In the U.S. alone, there are 50 million people who smoke cigarettes (2). Many smokers will not quit and are expected to continue the habit for the rest of their lives. Among tobacco-caused cancer, lung cancer has been the leading cause of death in males in the U.S., and recently it has surpassed breast cancer in cancer mortality in females (3). This tragedy is expected to be repeated in many developing countries such as China due to a sharp increase in the prevalence of cigarette smoking in recent years. Of course the best way to eradicate lung cancer is to stop smoking. However, it is difficult to effectively modify the life style in a large population. Therefore, there is an imminent need to identify chemopreventive agents, both natural and synthetic, to counteract the carcinogenic action of smoking. Numerous agents in cigarette smoke are found to be carcinogenic (4). The most intriguing 0097-6156/92/0507-0300$06.00/0 © 1992 American Chemical Society
Huang et al.; Phenolic Compounds in Food and Their Effects on Health II ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
23.
CHUNG ET AL.
301
Protection Against Lung Tumorigenesis
ones are the tobacco-specific alkaloid-derived nitrosamines. They are abundant, and some of them are potent carcinogens in laboratory animals (J). The most potent among them in 4-(methylnitrosamino) l-(3-pyridyl)-l-butanone (NNK), a nicotine-derived nitrosamine (Figure 1), which is highly specific for the induction of lung tumor in various animal species (5). The organospecificity of N N K toward lung is independent of the route of administration. Due to its potency and organotropism, it is believed that N N K may be one of the compounds in tobacco, i f not the major one, responsible for the development of lung cancers in smokers. In this chapter we will describe our recent work regarding the effects of green tea and its components on the lung tumor formation induced by N N K .
Downloaded by CORNELL UNIV on July 31, 2016 | http://pubs.acs.org Publication Date: October 1, 1992 | doi: 10.1021/bk-1992-0507.ch023
Modification of N N K Lung Tumorigenesis by Diet The carcinogenic effect of N N K has been shown to be influenced by dietary components. We have observed a different response in the formation of lung tumor induced by N N K depending on the types of diet used in the A / J mouse bioassay. Mice fed a crude cereal-based diet (NIH-07) developed an average of 2.5 lung tumors per mouse as compared to an average of 8.3 tumors per mouse in mice fed a semipurified diet (AIN-76A) (
