Inhibition of Lung Carcinogenesis by Black Tea in Fischer Rats Treated with a Tobacco-specific Carcinogen: Caffeine as an Important Constituent

Abstract Here, we examined the effect of black tea and caffeine on lung tumorigenesis in F344 rats induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in a 2-year bioassay. NNK was administered s.c. at a dose of 1.5 mg/kg body weight three times weekly for 20 weeks. Animals were given either black tea as drinking water at concentrations of 2%, 1%, or 0.5%, or caffeine in drinking water at concentrations identical to those in 2% and 0.5% tea infusions for 22 weeks. The treatment period began 1 week before and ended 1 week after the NNK administration. The animals were sacrificed on week 101 for the examination of tumors in target organs, including lung, liver, nasal cavity, and other major organs. The NNK-treated group, given 2% black tea, showed a significant reduction of the total lung tumor (adenomas, adenocarcinomas, and adenosquamous carcinomas) incidence from 47% to 19%, whereas the group given 1% and 0.5% black tea showed no change. The 2% tea also reduced liver tumor incidence induced by NNK from 34% in the group given only deionized water to 12%. The tumor incidence in the nasal cavity, however, was not affected by either black tea or caffeine at any of the concentrations tested. The most unexpected finding was the remarkable reduction of the lung tumor incidence, from 47% to 10%, in the group treated with 680 ppm caffeine, a concentration equivalent to that found in the 2% tea. This incidence is comparable to background levels seen in the control group. This study demonstrated for the first time in a 2-year lifetime bioassay that black tea protects against lung tumorigenesis in F344 rats, and this effect appears to be attributed, to a significant extent, to caffeine as an active ingredient of tea.