Antitumor Effect of Green Tea on Rat Urinary Bladder Tumor Induced by

Chapter 19

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Antitumor Effect of Green Tea on Rat Urinary Bladder Tumor Induced by N-Butyl-N-(4-hydroxybutyl) nitrosamine M. Matsushima and D. Sato Second Department of Urology, School of Medicine, Toho University, Tokyo 153, Japan

The effect of various types of tea, including leaf and powdered green tea, on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis in rats were investigated. Green tea had an antitumorgenic effect on urinary bladder tumor induced in rats by B B N , while halffermented tea (oolong tea) and fermented tea (black tea) did not. Powdered green tea had a concentration-dependent effect on urinary bladder tumor, and the antitumorgenic effect of powdered green tea was pronounced than that of leaf green tea. The incidence of urinary bladder cancer in Japan is very low compared with that in the USA. However, the urinary bladder cancer rate in 3rd generation, or later, JapaneseAmericans in about 3 times that of native Japanese (1). a number of contributing environmental factors has been identified in the case of bladder cancer. Of that, the role of diet is very important in urinary bladder carcinogenesis. Green tea has a long history, and its therapeutic effects have been frequently reported. Recently, attention has been paid to the anti-carcinogenic effect of its principal ingredient, cathechin (2). In the present study, we investigated the inhibitory effect of the various types of tea, including green tea, on the carcinogenesis of urinary bladder tumors induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Materials and Methods First Experiment. Fifty-seven weeks old male Wistar rats divided into two groups, and B B N was added to their drinking water for 5 weeks at a concentration of 0.05%. The drinking water was then replaced with tap water for the control group and sencha (green tea) for the green tea group.

©1998 American Chemical Society

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Second Experiment. One hundred and twenty-seven weeks old male Wistar rats were used. We divided them into 6 groups and B B N was added to their drinking water for 5 weeks at a concentration of 0.05%. At the beginning of week six, the drinking water was replaced by ordinary tap water for the control group (group 1), sencha (green tea) for group 2, macha for group 3, hojicha (roasted green tea) for group 4, oolong tea for group 5, and black tea for group 6. Methods of Tea Preparation. Sencha and Hojicha: We poured 1200 mL of hot tap water on 10 g tea leaves of commercially available sencha and hojicha. After 60 seconds, the decoction was cooled to room temperature and given as drinking water to the animals. Macha: We poured 400 mL of hot water on 10 g of the commercially available macha. After whipping, the decoction was diluted 100 times and given as drinking water to the animals. Oolong tea and black tea: We poured 100 mL of hot tap water on a tea pack of commercially available oolong tea or black tea. After 3 min, the decoction was cooled to room temperature and given as drinking water to the animals. Third Experiment. One hundred seven weeks old male Wistar rats were used. We divided them into five groups, and B B N was added to their drinking water at a concentration of 0.05% for 5 weeks. After that, the drinking water was replaced with tap water. The control group was fed a CE-2 pellet diet (by Nippon Clea Co.), group 2 was fed 0.15% powdered green tea CE-2 pellet diet, group 3 a 1.5% powdered green tea CE-2 pellet diet, group 4 a 3% powdered green tea CE-2 pellet diet and group 5 a 6% powdered green tea CE-2 pellet diet for 40 weeks. Results First Experiment. A l l rats were sacrificed at 40 weeks and their urinary bladders were distended with 10% formaldehyde solution and a ligature placed around the neck of each bladder to maintain proper distention. After fixation, the number of gross tumors was counted and the size of each tumor measured by ruler. The bladder was then sliced and prepared for light microscopy. Tissues were embedded in paraffin and stained with hematoxyline and eosin. Gross tumors were nearly all spherical papillary tumors like that shown in Fig. 1-3. Regarding the mean volume per tumor and total tumor volume, there were significant differences between groups. However, there were no significant differences between groups in the number of rats with tumors or the number of tumors per rat. The body weight of the rats was nearly identical in both groups, with no side effects noted. The results indicate that oral administration of green tea suppresses the growth of BBN-induced bladder tumors in rats (Fig. 4). Second Experiment. A l l rats were sacrificed at 40 weeks. Regarding the number of tumors per rat, there were significant differences between the green tea and roasted tea groups and the control group. However, there were no significant differences between the macha, oolong tea, and black tea groups, and the control group. There were also significant differences in mean tumor volume per rat between the green tea and control group. The total tumor volume of the green tea group was one tenth that of the control groups. In this experiment, green tea had an antitumor effect on B B N induced urinary bladder tumors in rats. However, the half-fermented tea (oolong tea) and fermented tea (black tea) did not have such an effect (Fig. 5). T h i r d Experiment. A l l rats were sacrificed at 40 weeks. Tumor incidence in groups 1, 2, 3, 4, and 5 was 96%95%, 75%, 88%, and 92%, respectively.


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Fig. 1. Normal urinary bladder of Wistar rat.

Fig. 2. Urinary bladder tumor of the control group.


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Fig. 3. Urinary bladder tumor of the green tea group.

100 75 50 25 0 rats with gross tomor (%)

No. of tumors per rat

p

Antitumor Effect of Green Tea on Rat Urinary Bladder Tumor Induced by

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