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ABSTRACT: Tea is one of the most frequently consumed beverages in the world, second only to water. Epidemiological studies have associated the consumption of green tea with a lower risk of several types of cancers, including stomach, oral cavity, esophagus, and lung. This paper deals with the mechanism of action of tea as an effective chemopreventive agent for toxic chemicals and especially carcinogens. UDP-glucuronosyltransferase (UDP-GT) activities towards p-nitrophenol were markedly increased (51.8% or 1.5-fold) in rats that consumed tea compared with the control animals on water. Induction of UDP-glucuronosyltransferase activity by tea may involve the UDP-GT1 (UGT1A) gene complex of the UDP-GT multigene family. Therefore, a major mechanism of tea as a chemopreventive agent is induction of the microsomal detoxification enzyme, UDP-glucuronosyltransferase.
Food and Chemical Toxicology 07/2002; 40(6):841-4. · 3.00 Impact Factor
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ABSTRACT: Methylazoxymethanol (MAM) and its chemical and metabolic precursor, azoxymethane (AOM), both strong colon carcinogens in rodents, can be metabolically activated by CYP2E1 in vitro. Using CYP2E1-null mice, we found that CYP2E1 deficiency differentially affects the activation of AOM and MAM, as reflected in DNA guanine alkylation in the colon and in the formation of colonic aberrant crypt foci (ACF). Male and female inbred 129/SV wild-type (WT) and CYP2E1-null (null) mice were treated with 189 micromol/kg of either AOM or methylazoxymethyl acetate (MAMAc), and 7-methylguanine (7-MeG) and O(6)-methylguanine (O(6)-MeG) were measured in the DNAs of various organs. The levels of O(6)-MeG (as pmol/nmol guanine) in the liver, colon, kidney, and lung of male null mice treated with AOM were 87, 48, 70, and 43% lower, respectively, than in AOM-treated WT mice. In null mice treated with MAMAc, the DNA O(6)-MeG levels were lower by 38% in the liver but were higher by 368, 146, and 194% in the colon, kidney, and lung, respectively, compared with the same organs of WT mice treated in the same way. Determination of ACF revealed that although AOM-induced ACF formation was significantly lower in the null group than in the WT group, MAMAc-induced ACF formation was significantly higher in the null group than in the WT group. These results demonstrate an important role for CYP2E1 in the in vivo activation of AOM and MAM and suggest that agents that modify CYP2E1 activity at the tumor initiation stage might either enhance or inhibit colon carcinogenesis, depending on whether AOM or MAMAc is used as the carcinogen. The mechanism of this effect is discussed.
Cancer Research 01/2002; 61(23):8435-40. · 7.86 Impact Factor
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J H Weisburger
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ABSTRACT: We have explored the causes of the major chronic diseases prevailing in the world and the relevant mechanisms as a sound basis for recommendations for their prevention. Research shows that the cocoa bean, and tasty products derived from the cocoa bean such as chocolate, and the beverage cocoa, popular with many people worldwide, is rich in specific antioxidants, with the basic structure of catechins and epicatechin, and especially the polymers procyanidins, polyphenols similar to those found in vegetables and tea. Metabolic epidemiological studies indicate that regular intake of such products increases the plasma level of antioxidants, a desirable attribute as a defense against reactive oxygen species (ROS). The antioxidants in cocoa can prevent the oxidation of LDL-cholesterol, related to the mechanism of protection in heart disease. Likewise, a few studies show that ROS associated with the carcinogenic processes is also inhibited, although there have not been many studies on a possible lower risk of various types of cancer either in humans or in animal models consuming cocoa butter or chocolates. Based on the knowledge acquired thus far, it would seem reasonable to suggest inhibition of the several phases of the complex processes leading to cancer, as a function of quantitative intake of antioxidants, including those from cocoa and chocolates. Cocoa and chocolate also contain fats from cocoa butter. These are mainly stearic triglycerides (C18:0) that are less well absorbed than other fats, and are excreted in the feces. Thus, cocoa butter is less bioavailable and has minimal effect on serum cholesterol.
Experimental Biology and Medicine 12/2001; 226(10):891-7. · 2.64 Impact Factor
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J H Weisburger
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ABSTRACT: Observations on cancer causation are some 150 years old, but actual detailed research on elements bearing on cancer started at the beginning of the twentieth century. Rapid progress, however, is only some 40 years old. Studies in humans documented certain lifestyle related factors to lead to cancer, and research in animal models strengthened this information. With the realization that there are carcinogens that in a metabolically activated attack DNA, in contrast to other agents that act by promoting, enhancing processes through totally distinct mechanisms, it became possible to develop and apply tests for DNA reactivity, in a prokaryotic organism, the widely used Salmonella typhimurium test by Ames and in a eukaryotic system, namely freshly explanted liver cells displaying evidence of DNA repair by Williams. A battery of these two tests are over 90% accurate in defining genotoxicity. Virtually all documented human carcinogens are genotoxic. With advances in molecular biology, mutational events are traced to changes in tumor suppressor genes or in oncogenes, that can serve as markers of risk. In addition, reactive oxygen systems (ROS) are involved in both the early steps in cancer and in the developmental aspects. Thus, foods containing antioxidants such as vegetables, fruits, soy products, cocoa and tea that counteract ROS are protective in cancer causation and development. Worldwide application of current knowledge and mechanisms to cancer prevention, the definitive means of cancer control, is likely to lower not only cancer but also heart disease risk in the current century.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/2001; 480-481:23-35. · 2.85 Impact Factor
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ABSTRACT: The effects of green tea on the metabolism of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) with emphasis on the formation of the detoxified glucuronides was studied. Two groups of 20 adult male and female Fischer 344 rats consumed 2% green tea or water for 6 weeks before being administered a single dose of 40 mg/kg body weight of [2-14C]IQ by oral gavage. Major metabolites in 24 h urine samples were separated by high-performance liquid chromatography (HPLC), including N-OH-IQ-N-glucuronide, 5-OH-IQ glucuronide and sulfate, IQ sulfamate and IQ itself. The structures of the main metabolites were established by mobility on the HPLC and by mass spectrometry. Sulfate esters and sulfamate were hydrolyzed by 0.1 N HCl for 15 min at 100 degrees C, yielding 5-OH-IQ and high levels of IQ. HPLC of the resulting product showed the N-OH-IQ-N-glucuronide and the 5-OH-IQ glucuronide, as well as IQ. The male and female rats drinking tea displayed a significantly higher (P < 0.05) excretion of the two major glucuronides. We conclude that intake of green tea increases the excretion of N-OH-IQ-N-glucuronide, a detoxified metabolite of the proximate carcinogen N-OH-IQ.
Carcinogenesis 07/2001; 22(7):1095-8. · 5.70 Impact Factor
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ABSTRACT: The effects of green tea intake on the metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the rat was studied. IQ belongs to a new class of mutagens and carcinogens, heterocyclic arylamines, formed during cooking through browning meats and fish, thus, in the food chain of most non-vegetarians. Ten adult male and female Fischer 344 rats were placed on a 2% solution of green tea and 10 control rats were on water for 6 weeks. Then, animals were administered a single dose of 40 mg/kg body weight of [2-14C]IQ by oral gavage. Twenty-four hour urine samples were collected and metabolites were separated by HPLC and quantitated by scintillation counting. Two minor and three major metabolites were isolated, including, small quantities of IQ itself. The rats on tea showed significant differences (P < 0.05) in the recovery of the three major metabolites, namely, IQ-sulfamate, IQ-5-O-sulfate, and IQ-5-O-glucuronide, respectively. Green tea, therefore, influences the manner in which the food carcinogen IQ is metabolized and excreted in urine. Formation of glucuronides, increased by green tea, represent a key means of detoxification of the heterocyclic amine, IQ.
Food and Chemical Toxicology 06/2001; 39(6):629-33. · 3.00 Impact Factor
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ABSTRACT: Coronary heart disease and many types of cancer are important diseases in the world and especially in Western countries. There are biochemical activation processes for low-density lipoprotein cholesterol and genotoxic carcinogens to reactive products. In part, these also involve the generation of active oxygen and reactive oxygen species. We investigated the effect of a natural product, MitoLife, which contains a mixture of fruit and tea extracts, on the oxidation of low-density lipoprotein cholesterol and the mutagenicity of five genotoxic carcinogens, specifically, 2-acetylaminofluorene, 2-aminoanthracene, 2-amino-3-methylimidazo[4,5-f]quinoline, aflatoxin B(1), and benzo[a]pyrene. A positive antioxidant control, polyphenon 60, a concentrate of green-tea polyphenols, was used to compare the effect of MitoLife with that of polyphenon. MitoLife displayed inhibiting effects in all series of tests at slightly lower effectiveness but with the same order of magnitude as the green-tea polyphenol product. Thus, MitoLife represents another means to decrease adverse effects associated with the oxidation of low-density lipoprotein cholesterol or of a series of carcinogens, some of which are in the human environment.
Nutrition 05/2001; 17(4):322-5. · 3.03 Impact Factor
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J H Weisburger
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ABSTRACT: Most of the prevailing chronic diseases in the world have an important nutritional component by directly causing a specific disease, enhancing the risk through phenomena of promotion, exerting a beneficial effect in decreasing risk, or preventing the disease. International studies in geographic pathology have shown that a given disease may have vastly different incidence and mortality as a function of residence. Laboratory research in animal models can reproduce fairly accurately what is learned through international research and provide the basis for examining relevant hypotheses and, more importantly, proposed mechanisms of action. Validation of these approaches can be the basis for public-health recommendations and health-promotion activities. Through such techniques, it has been found that regular intake of foods with saturated fats such as meat and certain dairy products raise the risk of coronary heart disease. The total mixed-fat intake is associated with a higher incidence of the nutritionally linked cancers, specifically cancer of the postmenopausal breast, distal colon, prostate, pancreas. ovary, and endometrium. The associated genotoxic carcinogens for several of these cancers are heterocyclic amines, which also play a role in heart-disease causation, and these are produced during the broiling and frying of creatinine-containing foods such as meats. Monounsaturated oils such as olive or canola oil are low-risk fats as shown in animal models and through the observation that the incidence of specific diseases is lower in the Mediterranean region, where such oils are customarily used. High salt intake is associated with high blood pressure and with stomach cancer, especially with inadequate intake of potassium from fruits and vegetables and of calcium from certain vegetables and low-fat dairy products. Vegetables, fruits, and soy products are rich in antioxidants that are essential to lower disease risk stemming from reactive oxygen systems in the body. Green and black teas are excellent sources of antioxidants of a polyphenol nature. as is cocoa and some chocolates. Nutritional lifestyles that offer the possibility of a healthy long life can be adopted by most populations in the world.
Nutrition 10/2000; 16(9):767-73. · 3.03 Impact Factor
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J H Weisburger
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ABSTRACT: Much progress has been achieved by exploring the causes of the main human cancers and of cardiovascular and cerebrovascular diseases. Even more important has been the knowledge acquired about the mechanisms underlying the development of these diseases. In many parts of the world, particularly in the West, the major cancers associated with dietary habits involve the postmenopausal breast, distal colon, prostate, pancreas, ovary, and endometrium. Current evidence suggests that the genotoxic carcinogens for all but the last 2 of these diseases stem from the traditional intake of fried and broiled foods such as meats. The surface of these foods contains a class of powerful mutagens, heterocyclic amines, which are carcinogenic to the target organs in animal models. Fish-eating populations have lower incidences of heart disease and of many types of cancers than do other populations, which may be the result of the n-3 polyunsaturated oils found in fish. Among other dietary practices that may reduce the risk of cancer and cardiovascular disease are consuming 5-9 servings of fruits and vegetables daily, which provides antioxidants such as quercetin and isothiocyanates; having a high fiber intake, including bran cereal; and drinking 1.5-2.5 L of fluids daily. Tea polyphenols found in black and green tea may have a protective effect against heart disease and some cancers. Concentrates of such desirable products have been made available in pill form to complement health-promoting personal lifestyles. Biomedical research funded by The National Institutes of Health and organizations such as the American Cancer Society has produced sound results that could lead to prevention of chronic disease. The public must heed this information to achieve long-term health.
American Journal of Clinical Nutrition 07/2000; 71(6 Suppl):1710S-4S; discussion 1715S-9S. · 6.67 Impact Factor
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J H Weisburger
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ABSTRACT: The transformation of normal cells by DNA reactive, genotoxic carcinogens and the growth promotion and development of mutated cells by enhancing factors is involved in the overall basic mechanism of cancer induction. Thus, discrimination between genotoxic carcinogens and nongenotoxic chemicals is essential. The dose-response curves, reversibility, and organ-and species specificity are distinct. Genotoxic carcinogens are mutagenic, form DNA adducts, induce DNA repair, and form hydroxy radicals and inappropriate peroxidation reactions that antioxidants such as those in vegetables, fruits, and tea can decrease. In contrast, promoters do not form DNA adducts, but raise cell duplication rates, among other attributes. In the USA, about 35% of known cancers are associated with tobacco use and about 55% with inappropriate nutritional habits. Cancer induction can be decreased by avoiding the formation of carcinogens, reducing their metabolic activation, or increasing their detoxification. Excessive dietary salt, and heterocyclic arylamines formed in cooking of meats or fish, and high intake of 40% of calories in fats are health risks, but vegetables, fruits, tea, soy products, and fibers are protective. We review nutritional factors involved in cancer and chronic disease causation and prevention.
BioFactors 02/2000; 12(1-4):73-81. · 4.93 Impact Factor
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J H Weisburger
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ABSTRACT: Cancer is a dread disease worldwide. Mortality of individuals suffering from cancer is high, despite the current improved methods of precocious detection, surgery and therapy. Prevention of cancer is the recognized goal of many activities in cancer research. This aim was recognized early to involve the bioassay of environmental chemicals or mixtures. The first such study involved application of coal tar to the ear of rabbits, and later on to the skin of mice. Subsequently, laboratory rats were introduced, and hamsters were utilized as a substitute for the unwieldy tests in rabbits. Investigators also became concerned with the mechanisms of carcinogenesis, and more definitive approaches to carcinogen bioassay in laboratory animals, as possible indicators of cancer risk in humans. These tests were expensive and lengthy, and did not serve the important purpose of accurately measuring risk of cancer to humans. Once it was realized that DNA and the genetic apparatus might be a key target, rapid bioassays in bacterial and mammalian cell systems were introduced successfully. Thus, batteries of tests are now available to detect effectively human cancer risks, and provide novel approaches to determine the underlying mechanisms, as a sound basis for cancer prevention.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/1999; 437(2):105-12. · 2.85 Impact Factor
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V E Steele,
D Bagheri,
D A Balentine,
C W Boone,
R Mehta,
M A Morse,
S Sharma,
C C Sigman,
G D Stoner,
M J Wargovich, J H Weisburger,
S Zhu,
G J Kelloff
Proceedings of The Society for Experimental Biology and Medicine 05/1999; 220(4):210-2.
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J H Weisburger
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ABSTRACT: Detailed multidisciplinary research on the effect of tea and the associated tea polyphenols has led to major advances on the underlying mechanisms. In most studies, green and black tea have similar effects, four of which are reviewed in this paper. 1) Tea polyphenols are powerful antioxidants that may play a role in lowering the oxidation of LDL-cholesterol, with a consequent decreased risk of heart disease, and also diminish the formation of oxidized metabolites of DNA, with an associated lower risk of specific types of cancer. 2) Tea and tea polyphenols selectively induce Phase I and Phase II metabolic enzymes that increase the formation and excretion of detoxified metabolites of carcinogens. 3) Tea lowers the rate of cell replication and thus the growth and development of neoplasms. 4) Tea modifies the intestinal microflora, reducing undesirable bacteria and increasing beneficial bacteria. The accumulated knowledge suggests that regular tea intake by humans might provide an approach to decrease the incidence of and mortality from major chronic diseases.
Proceedings of The Society for Experimental Biology and Medicine 05/1999; 220(4):271-5.
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ABSTRACT: The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-beta]pyridine NPhIP) is a major dietary component in individuals eating cooked meats or fish. This heterocyclic amine requires biochemical activation, mainly through cytochrome P4501A2, and can be detoxified chiefly by 4'hydroxylation through other cytochromes, and be in turn converted through phase 2 enzymes to readily excreted conjugates. The active form of PhIP is mutagenic in Salmonella typhimurium TA98 and is a useful substrate to study the possible chemoprotective action of phytochemicals. We found that black and green tea depressed the mutagenicity of PhIP in dose-related fashion, and decaffeinated tea was less powerful an inhibitor. This led to the study of caffeine, that displayed effective dose-related inhibition of the mutagenicity of PhIP. Other antioxidants such as lycopene, the active antioxidant from tomatoes, and daidzein and genistein from soy products, also had a dose-related inhibition of the mutagenicity of PhIP. We conclude that PhIP is a good substrate found in several human foods to determine the protective effect of phytochemicals from vegetables, and beverages.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 09/1998; 416(1-2):125-8. · 2.85 Impact Factor
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J H Weisburger
Proceedings of The Society for Experimental Biology and Medicine 07/1998; 218(2):93-4.
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J H Weisburger
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ABSTRACT: During the last 30 years, research in the field of nutrition and chronic disease causation has led to exciting, significant progress in providing an understanding of specific risk factors and chemopreventive agents. The major health problems considered are cardiovascular diseases and the nutritionally linked cancers, including those in the stomach, colon, breast, prostate, ovary, and endometrium. The major elements considered were salt, type and amount of fat, and heterocyclic amines formed during cooking. Bran cereal fiber, as well as vegetables, fruits, and tea have been shown to inhibit the complex processes of initiation and development of these diseases. One aspect involved in initiation and development of both cardiovascular diseases and the cancers noted are abnormal oxidative processes leading to the generation of hydroxy radicals and peroxy compounds. In part, the protective role of vegetables, fruits, and tea is to provide antioxidant vitamins and specific polyphenols that display a powerful inhibition in oxidative reactions. Epidemiological studies as well as laboratory experimentation have yielded sound data and evidence in support of the fact that vegetables, fruits, and tea and specific antioxidants therein account mechanistically for inhibition. Geographic pathology has provided important data that populations with a regular intake of tomato products, such as in the Mediterranean region, have a lower incidence of the chronic diseases noted. The current Symposium is considering the varied mechanisms of action of tomato products in general, and one of the active principles, lycopene. Cooking is a factor in releasing the desirable antioxidants from tomatoes. Cooked tomato products may be preferable to the raw vegetable or juices derived from tomatoes bearing on absorption of the active principles. Optimally, absorption of lycopene, a highly lipid-soluble chemical, is improved in the presence of a small, but essential amount of oil or fat. Research in the field of nutrition and health has shown that monounsaturated oils such as olive oil or canola oil are most desirable, since such oils do not increase the risk of atherosclerosis, coronary heart disease, or the nutritionally linked cancers. The International Symposium on tea conducted in 1991 has provided worldwide interest in research on the beneficial effects of tea. It is now hoped that the present Symposium, dealing with another inexpensive and readily available food, tomatoes, will enhance interest in and funding for additional research, to underwrite future recommendations for possibly enhanced production and use of tomato-derived nutritional elements, with the goal of application to the prevention of major chronic diseases, the treatment of which is costly and often ineffective.
Proceedings of The Society for Experimental Biology and Medicine 07/1998; 218(2):140-3.
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J H Weisburger
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ABSTRACT: International research, particularly as part of US/Japan programs, has led to major advances in knowledge of causes of heart disease, stroke, many types of cancer and diabetes, showing that individual lifestyle is associated with these diseases. In Japan, a major health problem is high blood pressure and stroke, and cancer of the stomach, from excessive use of salt and salted, pickled foods, and the relative low intake of protective fruits and vegetables. We identified a likely gastric carcinogen, 2-chloro-4-methylthiobutanoate, in salted, pickled fish. In the Western world, heart disease and cancer of the breast, colon, rectum, prostate, pancreas, ovary and endometrium relate to a nutritional tradition too high in total fat and fried or broiled meats, and too low in fiber, vegetables and fruits. The cooked meats contain genotoxic chemicals, heterocyclic amines, causative elements in heart disease and the nutritionally linked cancers. Decreasing total fat intake, from 40 to 20% of calories and a greater use of starches such as rice, pasta, potatoes and whole grain bread, as well as daily intake of five to nine vegetables and fruits would be beneficial. Adults should consume 2.5 l of fluids per day. Green or black tea and fruit juices have health promoting properties. Regular exercise contributes to good health, and to the avoidance of obesity, a major problem in the USA and of increasing importance in Japan. Avoidance of a risky lifestyle would likely prevent diseases important not only for the individual and his family, but with major impact in lowering medical care costs. Tobacco and cigarette use, particularly on a Western diet, involve a high risk of heart attacks, and cancers of the lung, pancreas, kidney, urinary bladder, and cervix, accounting for 35% of medical care expenditures.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 07/1998; 402(1-2):331-7. · 2.85 Impact Factor
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ABSTRACT: Studies were conducted to determine the chemopreventive efficacy of several types of tea extracts on azoxymethane-induced colon cancer in male F344 rats. After determining the maximally tolerated dosage of the tea products, their effect in a colon cancer model was investigated. Groups of 36 male F344 rats received 2 subcutaneous doses of 15 mg/kg azoxymethane (AOM) at Weeks 6 and 7. Experimental groups also received as drinking fluids 3600 ppm of black or green tea extracts, 1800 ppm of EGCG, or 1800 ppm of black or green tea polyphenols beginning at 5 weeks of age. Additional groups drank a lower dose of 360 ppm of the five tea products. The experiments were terminated 43 weeks after the first tea exposure. No evidence of toxicity was observed since the body weight gain of all groups was similar. The rats given AOM had carcinoma of the small intestine and of the colon, classified histologically as in situ carcinoma, exophytic, invasive, and Peyer's patch carcinoma. In the small intestine, most of the neoplasms were classified as invasive, but in the colon, most were exophytic. The various tea products failed to produce a significant difference in the incidence of the several types of colon and small intestine carcinoma. The multiplicity of colon cancers ranged from 1.2-2.8 in all groups. The group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the control group on AOM and water. Also, the group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the group on 360 ppm. The tea products did not affect the development aspects of the tumors in most groups. The mechanisms underlying these findings rest on the fact that azoxymethane is metabolized mainly by cytochrome P450 2E1, and this enzyme system is not affected by tea.
Proceedings of The Society for Experimental Biology and Medicine 02/1998; 217(1):104-8.
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ABSTRACT: 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.
Xenobiotica 02/1998; 28(2):213-7. · 1.79 Impact Factor
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ABSTRACT: Two sets of experiments on the role of tea in azoxymethane (AOM) induced colon cancer were performed. The first test involved male F344 rats given 1.25% solutions of black tea beginning at 5 weeks of age and ending at 51 days of age. At 6 and 7 weeks of age, they received 15 mg/kg AOM and were held for 50 weeks. Another group received the AOM dosage at 6 and 7 weeks and were placed on the tea solutions 2 days after the last AOM dosage, at 51 days of age, and held for the 50-week period. The end point was the occurrence and multiplicity of colon cancer, classified as in situ, exophytic, invasive and Peyer's patch carcinomas. Tea failed to affect the incidence and multiplicity of colon cancers when given during or after the AOM administration, but tea after AOM increased the multiplicity of exophytic carcinomas. In a second series of tests, solutions of 0.6, 1.25, 1.75 or 2.5% tea were given, beginning 1 week prior to the two AOM doses and extending for 42 weeks. Also, one group received 1.25% tea and 1.85% whole milk. The incidence of exophytic or invasive colon cancer and tumor multiplicity were similar in all treatment groups, although the incidence of exophytic neoplasms was higher with 2.5% tea. Thus, chronic administration failed to significantly change the incidence and multiplicity of the AOM-induced colon cancers. These findings are accounted for by the underlying mechanism, namely the fact that tea solutions do not alter the amount of cytochrome P-4502E1 required for the metabolic activation of AOM.
Carcinogenesis 02/1998; 19(1):229-32. · 5.70 Impact Factor
