Abstract 2761: Effect of DNA fragments and nucleotid supplementation on tumor development in mice model

Background: The balance of dNTP pool is needed for normal DNA synthesis. Nucleotide depletion can cause DNA damage thus it could lead to tumor development. The supplementation of substrates that are involved in DNA synthesis and methylation reactions could be a preventive step against oncogenic processes. Furthermore, tumor origin and heterogeneity could influence the cell response depend on experimental models (human SW480 versus animal-derived MCA38 colon adenocarcinoma). Aims: Our aims were to investigate the effect of elevated dNTP pool and modified DNA fragments on tumor growth, furthermore to detect the influence of different types of folates on tumor formation. Methods: C57BL/6 (n=35) mice with implanted MCA38 mouse colorectal adenocarcinoma cells were divided into 7 groups. Mice were injected subcutaneously on every 2nd days over 4 weeks in the doses of 10ug/animal with the following materials: dNTP (Group1) and methylated (d5mCTP) deoxynucleotide solution (Group2). In Group 3-5, mice were injected with artificially methylated and unmethylated spleen-derived DNA in different doses. Group 6 was supplemented with 20mg/kg folic acid orally, while saline (0.9% NaCl) was used as a vehicle in control group. In parallel, human-derived SW480 colon cancer cells (5 × 106) were injected subcutaneously on SCID mice (n=15). Xenograft mice were divided into 3 groups. 20mg/kg folic acid (Group A) and 20mg/kg L-methylfolate (Group B) were supplemented orally 5 times a week, as well as control mice were treated with saline. The length and width of the implanted tumors were measured with sliding calipers two times weekly by the same observer. Results: In the animal-derived (MCA38) tumor model, slower tumor developing tendency was observed in the dNTP supplementation group; d5mCTP supplementation moderately decreased tumor growth. Non-methylated DNA has also a concentration-dependent growth decreasing effect in MCA38 tumor development. However, folate supplementation has a different effect on tumor development based on the origin of the implanted colon tissue. Slower tumor developing tendency could be detected in the case of C57BL/6-C38 tumor model compared to controls, while folate supplementation stimulated the growth and proliferation of tumor cells in SW480-derived xenograft model (p