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


OBJECTIVE
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.


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).


CONCLUSIONS
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.
Pryzimirska
T V
TV
RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Science of Ukraine, Kyiv, Ukraine.
Pogribny
I P
IP
Chekhun
V F
VF
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D019175:DNA Methylation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006710:Homocysteine / Q000097:blood*; D015674:Mammary Neoplasms, Animal / Q000097:blood* / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D014408:Biomarkers, Tumor; D006710:Homocysteine