The impact of tumor growth on plasma homocysteine levels and tissue-specific DNAmethylation in Walker-256 tumor-bearing rats

Pryzimirska T.V., Pogribny I.P., Chekhun V.F.

Summary. Background: The elevation in plasma homocysteine (Hcy) concentrations has been associated with several types of human cancer; however, the major unanswered question whether or not hyperhomocysteinemia is associated with cancer pathogenesis and is an indicator of tumorigenesis, remains elusive. Aim: To define the impact of tumor growth on the levels of plasma Hcy and to elucidate the underlying mechanisms related to the tumor-associated hyperhomocysteinemia. Materials and Methods: Female Wistar rats were inoculated subcutaneously with Walker-256 mammary carcinoma cells. The dynamic of tumor growth, the concentrations of plasma Hcy, and status of DNA methylation in the livers and tumors in tumor-bearing rats were determined. Results: The results of our study demonstrated that development and progression of Walker-256 tumors is associated with both progressive hyperhomocysteinemia and tumor-specific genomic hypomethylation. The pattern of changes in the plasma Hcy concentrations was consistent with linear increase in DNA hypomethylation in tumors and with expansion of Walker-256 tumors. There was significant correlation of the concentrations of plasma Hcy with both parameters (r = 0.73 and r = 0.88, respectively; p < 0.05). Conclusion: The results of the study provided evidence that growth of Walker-256 tumors is associated with the increased levels of plasma Hcy. More importantly, these findings suggest that an underlying cause of hyperhomocysteinemia in tumor-bearing rats is related to the altered cellular methylation reactions in tumor cells and to tumor proliferation rate, and may serve as metabolic biomarker of cancer.

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