An experimental study of the prevention of pancreas cancer induced by N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian hamsters by green tea catechins (GTCs)
aUniversity of Shizuoka, Junior college, Shizuoka, Japan, bRedox Regulation Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
AIM It is well known that N-nirtosobis(2-oxopropyl)amine (BOP) induces the pancreas cancer in Syrian hamsters. And it is also well known that carcinogens cause the oxidative damages in their target tissues. In this study, the following were experimented: Whether BOP causes oxidative stress in the pancreas and whether Green tea catechins (GTCs) suppress the oxidative stress induced by BOP. And then the possibility of pancreas cancer prevention by Green tea catechins was examined. METHODS Six-week-old female Syrian golden hamsters were used. Hamsters were divided into two groups; one group was given free access to a 0.1% solution of GTCs as drinking water (c-ham) and the other to plain tap water (w-ham) in the interval to the end from 1 week before the weekly BOP subcutaneous injection (20mg/kg body weight) period. BOP injection was repeated 1, 3 or 6 times. Zero, 1, 2, 6, 12, 24 and 48 hours after the last BOP injection, the pancreas and liver were excised and the tissue concentration of lipid peroxides and/or the amount of 8-oxodG in nuclear DNA were measured. The tissue concentration of lipid peroxides was measured by the thiobarbituric acid (TBA) test and was corrected for the protein content of the tissue, which was determined by the Lowry method. Tissue nuclear DNA was treated with nuclease P1 and alkaline phosphatase after isolation from the tissue. The 8-oxodG content was determined with ECD-HPLC system. The results were assessed statistically by Student’s t test. In all instances, p values of <0.05 were considered statistically significant. REULTS The concentration of lipid peroxides and the amount of 8-oxodG showed similar patterns of change between c- and w-ham. In the pancreas exposed to BOP injection once, the concentration of lipid peroxides and the amount of 8-oxodG increased with a peak soon after BOP injection at 1 and 6 hours, respectively. And the peak values of c-ham were significantly depressed compared with those of w-ham and those peak levels returned to steady state levels by 24 hours. In w-ham, with the increase of the administration frequency of BOP, 8-oxodG steady state level tended to increase, and the value of the peak significantly increased, and the time to the recovery was lengthened. In c-ham, steady state level of 8-oxodG did not increase, even if the BOP administration frequency increased, and the rise of the peak value was also slight. In the liver which is not a target organ of BOP, the concentration of lipid peroxides and the amount of 8-oxodG were not affected by BOP administration. CONCLUSIONS 8-oxodG is not only a biomarker of DNA oxidative damage but also a predominant biomarker of carcinogenesis. In the present study, the increase of 8-oxodG in nuclear DNA of pancreas following BOP administration was observed. Moreover with the increase of the administration frequency of BOP, its effect for the pancreas tissue was escalated. And oral intake of GTCs showed a suppressive effect on those phenomena. These results suggest that GTCs have the possibility to prevent pancreas cancer.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 997 (Chemoprevention).