Abstract 2761: Effect of DNA fragments and nucleotid supplementation on tumor development in mice model
Authors: Nagy Zsófia Brigitta , Barták Barbara Kinga , Zsigrai Sára , Kalmár Alexandra , Szigeti Krisztina , Igaz Peter , Molnár Bela 
Published: September 2020

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&lt;0.05).

Conclusion: Our study described the effect of differently methylated DNA fragments and precursor molecules on the growth of tumor transplants. According to our results, tumor volume decrease was observed by providing sufficient DNA components to normal synthesis. Based on our results folate treatment has a different effect on cancer development regarding the tumor origin. Folate has a key role in nucleotide synthesis and also in DNA methylation therefore the selection of the appropriate dosing time is crucial.

Citation Format: Zsófia Brigitta Nagy, Barbara Kinga Barták, Sára Zsigrai, Alexandra Kalmár, Krisztina Szigeti, Peter Igaz, Bela Molnár. Effect of DNA fragments and nucleotid supplementation on tumor development in mice model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2761.