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 lung tumorigenesis by a group of characteristic black tea polyphenols, theaflavins. In a short-term study, female A/J mice were treated with a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 103 mg/kg b.w., i.p.) on day 0, and 0.1 and 0.3% theaflavins were administered as the sole source of drinking fluid starting 24 h after NNK treatment. The proliferation index of the lung tissues was measured by the incorporation of bromodeoxyuridine (BrdU) immunohistochemically. The highest NNK-induced proliferation rate of bronchiolar cells, observed on day 5, was significantly 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 16 after NNK treatment. Administration of theaflavins (0.1%) as the sole source of drinking fluid, starting 2 days after the NNK treatment until the termination of the experiment, significantly reduced the tumor multiplicity and 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 in lung adenomas was also significantly inhibited by theaflavins. The present work demonstrates the inhibitory action of theaflavins against NNK-induced pulmonary hyperproliferation and tumorigenesis.
Yang
G Y
GY
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, NJ 08855-0789, USA.
Liu
Z
Z
Seril
D N
DN
Liao
J
J
Ding
W
W
Kim
S
S
Bondoc
F
F
Yang
C S
CS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D044946:Biflavonoids; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D002392:Catechin; D002455:Cell Division / Q000187:drug effects; D018890:Chemoprevention; D005260:Female; D006965:Hyperplasia / Q000517:prevention & control; D008175:Lung Neoplasms / Q000139:chemically induced*; D051379:Mice; D008805:Mice, Inbred A; D009602:Nitrosamines / Q000037:antagonists & inhibitors*; D013662:Tea / Q000737:chemistry*; D014801:Vitamin A / Q000097:blood / Q000378:metabolism; D014810:Vitamin E / Q000097:blood / Q000378:metabolism
D000970:Antineoplastic Agents; D044946:Biflavonoids; D002273:Carcinogens; D009602:Nitrosamines; D013662:Tea; D014801:Vitamin A; D014810:Vitamin E; C056068:theaflavin; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D002392:Catechin; D001973:Bromodeoxyuridine