Date:   8/11/2006 10:47:14 PM ( 18 y ago)
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Tea drinking has been associated with decreased occurrence of cancer and heart disease. One potential mechanism for these findings is the strong antioxidant effect of tea polyphenols. A phase II randomized controlled tea intervention trial was designed to study the effect of high consumption (4 cups/d) of decaffeinated green or black tea on oxidative DNA damage as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG) among smokers over a 4-mo period. A total of 143 heavy smokers, aged 18–79 y, were randomized to drink either green or black tea or water. Levels of plasma and urinary catechins and urinary 8-OHdG were measured monthly. A total of 133 of 143 smokers completed the 4-mo intervention. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Plasma and urinary levels of catechins rose significantly in the green tea group compared with the other two groups. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a highly significant decrease in urinary 8-OHdG (-31%) after 4 mo of drinking decaffeinated green tea (P = 0.002). No change in urinary 8-OHdG was seen among smokers assigned to the black tea group. These data suggest that regular green tea drinking might protect smokers from oxidative damages and could reduce cancer risk or other diseases caused by free radicals associated with smoking.

KEY WORDS: • tea • smokers • DNA damage • 8-OHdG • trial

To protect human health from hazards caused by chronic exposure to environmental chemicals, it is recommended that antioxidants be taken daily in food or beverages.

Tea has received a great deal of attention because tea polyphenols are strong antioxidants, and tea preparations have shown inhibitory activity against tumorigenesis. Tea polyphenols, known as catechins, usually account for 30 to 42% of the dry weight of the solids in brewed green tea (1). The four major catechins are (-)-epigallocatechin gallate (EGCG),3 (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC). The major components of black tea (the fermented product) are theaflavins (1–3% dry weight) and thearubigins (10–40% dry weight). The potential health benefits associated with tea consumption have been partially attributed to the antioxidative property of tea polyphenols (2,3). The radical-quenching ability of green tea is usually higher than that of black tea (4). The chemical structures contributing to effective antioxidant activity of catechins include the vicinal dihydroxy or trihydroxy structure, which can chelate metal ions and prevent the generation of free radicals. This structure also allows electron delocalization, conferring high reactivity to quench free radicals (4–6).

Cigarette smoking is a known cause of lung cancer and other respiratory diseases. Cigarette smoke contains numerous compounds that generate reactive oxygen species that can damage DNA directly or indirectly (1) via inflammatory processes (5–7). Oxidants, either present in cigarette smoke and/or formed in the lungs of smokers, may trigger oxidative damage to DNA and cellular components, contributing to carcinogenesis. Free radical attack on DNA generates a multiplicity of DNA damage, including modified bases. Some of these modifications have considerable potential to damage the integrity of the genome. Although the quantitative relationship between the measured DNA damage and the development of cancer is lacking, evidence suggests that oxidants act at several stages in the malignant transformation of cells (8).

In the case of oxidative damage to DNA, damaged products are usually eliminated by repair enzymes and detected as nucleoside derivatives. Urinary 8-hydroxydeoxyguanosine (8-OHdG) is one adduct of this reaction and is proposed as a sensitive biomarker of oxidative DNA damage and repair (9–11). 8-OHdG is a relatively abundant and readily detected product of oxidative DNA damage and as such is regarded as a useful and relevant marker for cellular oxidative stress, particularly with respect to carcinogenesis (12,13). The argument has been made that oxidized adducts of DNA are promutagenic lesions. If they are not repaired, they can result in mutations. Changes in rates of mutation over a lifetime are expected to impact risk of malignancy.

Although direct evidence that links 8-OHdG with cancer risk is lacking, increased 8-OHdG has been found in cancerous tissues (14). Toyokuni et al. reported that human carcinoma cells (breast, lung, liver, kidney, brain, stomach, ovary) have a higher content of 8-OHdG than adjacent nontumorous tissues (15). Moreover, investigators have reported a high concentration of 8-OHdG in urine samples from patients with carcinoma of female genitalia (16), malignant breast tissues with invasive ductal carcinoma (14), colorectal tumor tissues (17), gastric cancer tissues (18) and lung cancer tissues (19). They hypothesized that the tumor cells themselves produce reactive oxygen species (ROS) spontaneously, which results in an increase of 8-OHdG in DNA.

Urinary excretion of 8-OHdG, the repair product from oxidative DNA modification by excision enzymes, is an in vivo measure of overall oxidative DNA damage (20). Urinary 8-OHdG is higher in small cell lung carcinoma patients compared with normal controls and increases in nonsmall cell lung carcinoma patients during the course of radiotherapy (21). Also, high oxidative stress, such as smoking or extreme exercise, is associated with high 8-OHdG production (22–24). In contrast to the analysis of 8-OHdG in DNA, its analysis in urine is more reproducible because of the lack of artifact formation, and the interlaboratory deviation seems to be low. Therefore, it should be easier to assess the effects of lifestyle factors, diet and genotoxic environmental chemicals on cellular oxidative stress by analyzing 8-OHdG in human urine (25).

Because cigarette smoking and tea drinking are very common behaviors in many diverse populations, several experimental studies have explored the possible inhibitory effects of tea on lung cancer formation induced by cigarette smoking (26–30). However, the effects of regular tea intake on 8-OHdG have not been fully examined in clinical trials. Therefore, we initiated a randomized controlled trial to test the efficacy of regular tea drinking in reducing DNA damage as measured by urinary 8-OHdG among heavy smokers. Furthermore, we sought to estimate the effectiveness of both black and green teas prepared and consumed in preparations readily available to consumers.


MATERIALS AND METHODS
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ABSTRACT
MATERIALS AND METHODS
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Study population

The study population consisted of 143 heavy smokers recruited between October 1999 and April 2001 in Tucson, Arizona. Healthy men and women smokers between the ages of 18 and 79 y were recruited in cohorts (n = ~36 smokers per cohort). Thirty-three men and 100 women completed the trial and were included in this analysis. All of the subjects were screened by questionnaire to exclude those who smoked <10 cigarettes per day (CPD) for <1 y, pregnant women, persons with a history of schizophrenia or cancer, current drug or alcohol abusers, individuals with an abnormal liver function blood test or those currently being treated with antidepressants. The study was approved by the Institutional Review Board of the University of Arizona, and all of the subjects provided informed consent before enrollment.

Study protocol

The study was a 3-arm randomized placebo-controlled tea intervention trial. Each individual was randomly assigned to drink 4 cups/d of decaffeinated green tea, decaffeinated black tea or water (Fig. 1). We provided each study participant with a 1-mo supply of the tea. Once a month for four months, study participants visited the clinic to 1) receive the monthly tea supply, 2) return completed tea and smoking diaries and 3) provide blood and urine specimens.

http://jn.nutrition.org/cgi/content/full/133/10/3303S

 

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