5-methyldeoxycytidine and Carcinogenesis

The methylation of the C-5 position of deoxycytidine (dC) in the promoter regions of tumor suppressor genes is often observed in cancer cells. We found that various environmental agents, as well as endogenous compounds such as methionine sulfoxide (MetO), generate methyl radicals and modify dC to form 5-methyl-dC in DNA in vitro. We confirmed that both DNA methylation and cancer incidence in the liver were increased by the administration of MetO to oxidatively stressed mice. In this review, we summarize previous reports on methyl radical generation in vitro and in vivo and DNA modifications by methyl radicals, including our discoveries, as well as our recent experimental evidence suggesting that free radical-mediated dC methylation triggers epigenetic changes.

Topics: Animals; Carcinogenesis; Deoxycytidine; DNA Methylation; DNA, Neoplasm; Epigenesis, Genetic; Humans; In Vitro Techniques; Methane

Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating events for cancer development.. The aim of the present study was to assess the effect of zinc and copper on the DNA methylation in rats whose breast adenocarcinoma was simultaneously induced with 7, 12 dimethylbenz[a]anthracene (DMBA). The research focused on the kinetics of alterations in urinary 5-MedC (5-methyl-2'-deoxycytidine) at the early and late stages of carcinogenesis, as well as the influence of dietary factors on the process.. The content of 5-methyl-2'-deoxycytidine in the rats' urine was determined by the ELISA (enzyme-linked immunosorbent assay) method. The 5-MedC level was standardized by conversion to the creatinine level.. It was found that in the rats fed only the standard diet and DMBA-treated the urinary levels of 5-MedC collected after the 10th week were considerably lower in comparison with the content of this biomarker in urine starting from the 19th week (43.56 ± 14.34 vs. 71.84 ± 42.64). The animals treated with DMBA and additionally obtaining copper were characterized by a much higher content of the examined biomarker in urine, both in the early phase of carcinogenesis (10th week) and later (19th week), as compared with the animals fed only the standard diet or the zinc-supplemented diet. In the rats with a fully developed tumor (100% incidence of the disease) the applied dose of resveratrol (0.2 mg/kg bw) was too low to prevent the intensive formation and increase of 5-MedC level in urine, additionally stimulated by the presence of Cu in the diet as well as by the active, ongoing neoplastic process.. Summing up the obtained results of investigations it can be said that the urinary level of 5-MedC depends on the applied supplementation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor; Carcinogenesis; Copper; Deoxycytidine; Dietary Supplements; DNA Methylation; Enzyme-Linked Immunosorbent Assay; Epigenomics; Female; Neoplasms, Experimental; Prognosis; Rats; Rats, Sprague-Dawley; Zinc