Abstract
Abstract AIM: The present study was designed to study the effect of different ratios of n-3 rich fish oil and n-6 rich corn oil in the prevention of colon cancer mediated through cell signaling and apoptosis. Methods: Male Wistar rats were divided into the following groups - Group-I and Group-II were fed synthetic diets and Group-III and Group-IV modified synthetic diets with 1:1 and 2.5:1 ratio of fish oil and corn oil for 4 weeks. All the groups except group-I (vehicle treated) received 4 injections of dimethyl hydrazine (DMH). The DMH injections were given after initiation on the synthetic diet for a week and subsequently received one injection per week. The animals were sacrificed 48 hrs after last injection. The last 10cm of the distal colon was used for histopathological study while the rest was used for isolation of colonocytes. The differential effect of the different ratios of oil on oxidative stress by measuring reactive oxygen species’(ROS) generation by FACS analysis using dichlorofluorescin diacetate (DCFH-DA) and p53 levels using monoclonal antibody was assessed. The apoptosis was evaluated by DNA fragmentation and by using M30 cytodeath antibody. To understand the role of mitochondria in apoptosis mitochondrial membrane potential was measured using JC-1. Akt levels were also measured using a monoclonal antibody in orderto understand its effect on p53 and apoptosis. Results: In the carcinogen administered animals as compared to the vehicle treated animals, there was- 1.mild to moderate inflammation 2. a decrease in ROS levels 3. a decrease in p53 4. an increase in apoptosis 5. an increase in mitochondrial membrane potential 6. an increase in Akt. Administration of fish oil and corn oil led to the following- 1. Fish oil feeding in the ratio 1:1 showed severe inflammation in the animals while feeding a higher ratio showed mild inflammation with normal mucosa. 2. a decrease in ROS levels with equal ratios as compared to the higher ratio of fish oil. 3. an increase in p53 levels with both the ratios 4. a decrease in apoptosis 5. a decrease in mitochondrial membrane potential 6. a decrease in Akt in equal ratios but a significant increase in the higher ratios. Conclusion: The results of the present study suggest that administration of fish oil in the higher ratio has a beneficial role in colon cancer as shown by histopathological examination. Fish oil derived n-3 PUFA exerts chemopreventive effect mediated by interplay among oxidative stress, apoptosis and cell survival signals depending on the dosage. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5716.
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