Einfluß von Vitamin A, C,und E auf die Lebermetastasierung beim BOP-induzierten Pankreaskarzinom des Syrischen Goldhamsters

Abstract

Background: Antioxidative vitamins are discussed in terms of their ability to inhibit neoplastic growth by influencing oxygen radical metabolism. However, it is still unclear whether vitamins may reduce liver metastasis as well. Therefore, we evaluated the impact of antioxidative vitamins A (retinol), C (ascorbic acid) and E (α-tocopherol) on liver metastasis in a solid experimental model of chemically induced ductal pancreatic adenocarcinoma in hamster. Methods: A total of 120 male Syrian hamsters were randomized into eight groups (n = 15). Group (Gr) 1 – 4 were given 0.5 ml normal saline s.c. weekly, whereas Gr 5 – 8 received 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kilogram of body weight s.c. per week for 3 months. In week 13 Gr 2 + 6 were administered retinol (0.25 mg/kg body weight/day), while Gr 3 + 7 received ascorbic acid (9 mg/kg body weight/day) and Gr 4 + 8 were given α-tocopherol (4 mg/kg body weight/day) orally. No therapy was performed in Gr 1 + 5. After 24 weeks animals were sacrificed and the incidence of pancreatic carcinoma and liver metastasis was determined histologically. Furthermore, activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), as well as the concentration of thiobarbituric acid reactive substances (TBARS) were analyzed in non-metastatic liver (NML), as well as in liver metastases (LiMe). Results: Retinol and a-tocopherol decreased the incidence of liver metastases (44.4% vs 86.7%, p < 0.05). Furthermore, the number and size of liver metastases were significantly reduced by retinol. Activities of GSH-Px and SOD were increased and the concentration of TBARS was decreased in NML and LiMe by all vitamins. Conclusion: Obviously, antioxidative vitamins prevent oxidative stress in hepatocytes caused by chemical carcinogenesis. This is possibly one mechanism which decreased liver metastasis in pancreatic cancer in the present trial.