Effects of green tea and black tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation, DNA methylation, and lung tumorigenesis in A/J mice.
Previous studies in our laboratory showed that decaffeinated green tea and black tea extracts inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced tumorigenicity in A/J female mice. In order to understand the mechanism of the inhibitory action, we examined the effects of decaffeinated green tea, black tea, and tea components on the metabolic activation of NNK in vitro and in vivo in this animal model. When added to incubation mixtures containing mouse lung microsomes, decaffeinated green tea and black tea extracts and their fractions, at concentrations up to 0.4 mg/ml, inhibited NNK oxidation and NNK-induced DNA methylation. Among the tea components examined, (-)-epigallocatechin-3-gallate was the most potent inhibitor with 50% inhibitory concentrations of about 0.12 mM for both NNK oxidation and DNA methylation. At these concentrations, (-)-epigallocatechin-3-gallate inhibited the catalytic activities of several P450 enzymes and was more potent against P450 1A and 2B1 than 2E1. When decaffeinated green or black tea extracts were given to female A/J mice as the sole source of drinking fluid before an i.p. injection of NNK (100 mg/kg body weight), a statistically significant inhibition of lung DNA methylation, however, was not observed, although a significant reduction in lung tumor multiplicity was observed. The results suggest that, although inhibition of the metabolic activation of NNK and the subsequent DNA alkylation by tea extracts can be demonstrated in vitro, this mechanism may not be important for the inhibitory action of tea against lung tumorigenesis.
Shi
S T
ST
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855-0789.
Wang
Z Y
ZY
Smith
T J
TJ
Hong
J Y
JY
Chen
W F
WF
Ho
C T
CT
Yang
C S
CS
D000818:Animals; D001628:Beverages; D002273:Carcinogens / Q000378:metabolism*; D002392:Catechin / Q000494:pharmacology / Q000031:analogs & derivatives; D004247:DNA / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced*; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D013662:Tea
D002273:Carcinogens; D005419:Flavonoids; D009602:Nitrosamines; D011725:Pyridines; D013662:Tea; C081510:4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D002392:Catechin; D004247:DNA; C057580:gallocatechol