Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice

The present study investigated the inhibitory activity against lungtumorigenesis by a group of characteristic black tea polyphenols,theaflavins. In a short-term study, female A/J mice were treated with asingle dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 103mg/kg b.w., i.p.) on day 0, and 0.1 and 0.3% theaflavins were administeredas the sole source of drinking fluid starting 24 h after NNK treatment. Theproliferation index of the lung tissues was measured by the incorporationof bromodeoxyuridine (BrdU) immunohistochemically. The highest NNK-inducedproliferation rate of bronchiolar cells, observed on day 5, wassignificantly decreased by 0.3% theaflavins (proliferation index, 1.51 +/-0.08 versus 2.35 +/- 0.16). In a long- term lung tumorigenesis study,pulmonary adenomas were observed in 100% (30/30) of the mice at week 16after NNK treatment. Administration of theaflavins (0.1%) as the solesource of drinking fluid, starting 2 days after the NNK treatment until thetermination of the experiment, significantly reduced the tumor multiplicityand volume by 23% (8.5 +/- 0.6 versus 6.5 +/- 0.6 tumors/mouse) and 34%(0.08 versus 0.05 mm3 per tumor), respectively. The proliferation index inlung adenomas was also significantly inhibited by theaflavins. The presentwork demonstrates the inhibitory action of theaflavins against NNK-inducedpulmonary hyperproliferation and tumorigenesis.