Aim: The present study was designed to study the chemopreventive effect of different ratios of n-3 PUFA rich fish oil and n-6 PUFA rich corn oil on prognostic markers, DNA damage and cell cycle phases in experimentally induced colon carcinoma.

Methods: Male Wistar rats were divided into control, dimethylhydrazine dihydrochloride (DMH) treated, FO+CO(1:1)+DMH and FO+CO(2.5:1)+DMH. All the groups, except control received a weekly injection of DMH for 4 weeks. The animals were sacrificed either 48 hrs later (initiation phase) or kept for 16 weeks (post initiation phase). The chemopreventive efficacy was evaluated by analyzing the regression of preneoplastic lesions, total sialic acid (TSA), lipid associated sialic acid (LASA). To study the underlying mechanisms DNA damage, distribution of cells in various phases of cell cycle, cyclin D1 and p53 levels were assessed in the isolated colonocytes.

Results: The animals treated with DMH in the initiation phase and post initiation phase studies showed increase in Multiple plaque lesions (MPL), total sialic acid (TSA), lipid associated sialic acid (LASA), DNA damage and cell proliferation with increased percentage of cells in G2M and S phase. However, levels of p53 and cyclin D 1 were not significantly altered in the initiation phase while levels were significantly elevated in the post initiation phase study on treatment with DMH.

The FO+CO(1:1)+DMH treatment in the initiation phase and post initiation phase led to a decrease in the MPL, DNA damage, TSA, LASA as compared to the control and DMH treated group. The cells were arrested in the G1 phase with a decrease in G2M and S phase. The levels of p53 and cyclin D1 were not significantly altered while a decrease in the levels was observed in the post initiation phase as compared to the DMH treated animals.

Treatment with FO+CO(2.5:1)+DMH in the initiation phase study and post initiation phase study led to a decrease in the MPL, TSA, LASA and DNA damage as compared to the DMH treated animals. The levels of p53 and cyclin D1 remain unaltered on treatment with FO+CO(2.5:1)+DMH in the initiation phase study. However a decrease was observed in the post initiation phase as compared to the DMH treated animals. The cells were arrested in the G1 phase in the initiation phase and revert to normal in the post initiation phase showing the protective effect. There was more protective effect in the FO+CO(2.5:1)+DMH treated animals as compared to the FO+CO(1:1)+DMH treated animals in the initiation phase and the post initiation phase showing the dose and time dependent effect of n-3 PUFAs.

Conclusion: The results of the present study suggest that fish oil and corn oil in the ration of 2.5;1 is more effective in chemoprevention of experimental colon carcinogenesis.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):A38.