Effect of tea on the formation of DNA adducts by azoxymethane.
1. The effect of black tea on the conversion of azoxymethane (AOM) to DNA reactive metabolites was studied in four groups of the male F344 rat. Each received 1.25% solutions of tea for 2 or 6 weeks, and simultaneous controls drank water. All rats were injected s.c. twice with 15 mg/kg AOM after the first or fifth week respectively, on tea or water, and again 1 week later. Groups were killed 6 h after the last dose, or 18 h later. The liver and colon were rapidly removed and rinsed with buffer solution, pH 7.0. DNA was isolated from these tissues, and DNA methylation was examined by the typical fluorescence of 06-methylated and N-7-methylated products, separated by HPLC. 2. Two or 6 weeks of tea intake failed to affect significantly the formation of alkylated DNA from liver and colon compared with controls drinking water. Only in the group of rats on tea for 6 weeks, and killed 6 h after the last dose of AOM, was the O6-methyldG and 7-methyldG decreased in DNA obtained from colon. 3. Thus, solutions of tea affected the formation of alkylated products in DNA of the colon of rats given AOM only at one time point, but did not do so under most other experimental conditions. The underlying mechanism is based on our previous finding that tea does not affect cytochrome P4502E1 that our group established to be the enzyme metabolizing AOM.
Chen
W
W
American Health Foundation, Valhalla, NY 10595-1599, USA.
Sohn
O S
OS
Fiala
E S
ES
Weisburger
J H
JH
D000478:Alkylation; D000818:Animals; D001397:Azoxymethane / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000502:physiology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013662:Tea / Q000502:physiology*
D018736:DNA Adducts; D013662:Tea; D006147:Guanine; C008450:7-methylguanine; D004247:DNA; C008449:O-(6)-methylguanine; D019392:Cytochrome P-450 CYP2E1; D001397:Azoxymethane