Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens.
Green tea contains catechins and caffeine as major constituents. Treatment of rats with green tea (2.5% w/v) significantly increased 7-ethoxycoumarin O-deethylase (7-ECOD), caffeine N-1 demethylase (CN1D) and UDP-glucuronyltransferase (UGT) activities. Treatment with caffeine similarly activated CYP1A2 and related monooxygenases as well as UGT, while treatment with catechins induced UGT activity but not 7-ECOD or CN1D activity. Numbers of benzo[a]pyrene (BP)-induced revertant colonies in an Ames test (mutation assay) with S. typhimurium TA98 as the test strain were markedly larger when BP was preincubated with the liver S-9 (9000 x g supernatant of liver homogenate) from green tea-treated rats than when preincubated with that from control rats. In a modified Ames assay system in which UGT was activated by the addition of UDP-glucuronic acid to the preincubation mixture, the numbers of revertant colonies in the assay using liver S-9 from green tea-treated rats decreased to a similar level to that in the assay using S-9 from controls. The acceleration of two enzymatic reactions may contribute to the rapid elimination of BP; the first step, the formation of a metabolic intermediate (which is mutagenic) by CYP1A2 and the second, the conjugation of active metabolic intermediates by UGT. We speculated that green tea can reduce the amount of time carcinogens reside in the body and the chance that body tissues will be exposed to active metabolites of carcinogens thorough rapid elimination due to the simultaneous induction of CYP1A2 and UGT activities.
Nikaidou
Satoshi
S
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Gradute School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Ishizuka
Mayumi
M
Maeda
Yutaka
Y
Hara
Yukihiko
Y
Kazusaka
Akio
A
Fujita
Shoichi
S
D000818:Animals; D016587:Antimutagenic Agents; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D002110:Caffeine / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013662:Tea
D016587:Antimutagenic Agents; D013662:Tea; D002110:Caffeine; D002392:Catechin; D001189:Aryl Hydrocarbon Hydroxylases; D014453:Glucuronosyltransferase