Free radical-mediated cytosine C-5 methylation triggers epigenetic changes during carcinogenesis

Aging is driven by unavoidable entropic forces, physicochemical in nature, that damage the raw materials that constitute biological systems. Single cells experience and respond to stochastic physicochemical insults that occur either to the cells themselves or to their microenvironment, in a dynamic and reciprocal manner, leading to increased age-related cell-to-cell variation. We will discuss the biological mechanisms that integrate cell-to-cell variation across tissues resulting in stereotypical phenotypes of age.

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“…In particular, spontaneous 5-methylcytosine methylation[8] and demethylation[9] are relevant to humans.…”

Section: Entropic Drivers Of Agingmentioning

confidence: 99%

Tissue aging: the integration of collective and variant responses of cells to entropic forces over time

Todhunter

Sayaman

Miyano

et al. 2018

Current Opinion in Cell Biology

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“…They tend to have hypomethylation overall, but hypermethylation in some genes in tumors. 33 In this study, the promoter DNA methylation levels of IL-4 and IFN-γ were found to be abnormal with contrary to mRNA expression. The results in this study also showed the decrease of genome-wide methylation rate (5-mC%) in rats' lung tissues in the PM 2.5 exposure group.…”

Section: Discussionmentioning

confidence: 53%

“…Global hypomethylation and regional hypermethylation are common mechanisms of aberrant expression of gene. They tend to have hypomethylation overall, but hypermethylation in some genes in tumors 33 . In this study, the promoter DNA methylation levels of IL‐4 and IFN‐γ were found to be abnormal with contrary to mRNA expression.…”

Section: Discussionmentioning

confidence: 55%

Vitamin B complex blocks the dust fall PM₂_.5‐induced acute lung injury through DNA methylation in rats

Bai

Tang

Luo

et al. 2022

Environmental Toxicology

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This study aimed to explore whether vitamin B complex (folic acid, B 6 , and B 12 ) could avert DNA methylation changes associated with inflammation induced by acute PM 2.5 exposure. Sprague-Dawley rats were administered by gavage with different concentrations of vitamin B complex once a day for 28 days, and then by intratracheal instillation with saline or PM 2.5 once every 2 days for three times. Vitamin B continued to be taken during the PM 2.5 exposure. Rats were sacrificed 24 h after the last exposure. The results showed that vitamin B complex could block the pathological changes and injury in lungs induced by PM 2.5 . Meanwhile, vitamin B complex could prevent the abnormal DNA methylation of IL-4 and IFN-γ to antagonize the imbalance of IL-4/IFN-γ associated with inflammation. It was further found that vitamin B complex could regulate DNA methyltransferases (DNMTs) and increase the Sadenosylmethionine (SAM)/S-Adenosyl-L-homocysteine (SAH) ratio to reverse the hypomethylation of genomic DNA and the abnormal DNA methylation of IL-4 and IFN-γ. In conclusion, vitamin B complex has a protective effect on acute lung injury by attenuating abnormal DNA methylation induced by PM 2.5 in rats. This study may provide a new insight into the physiological function of vitamin B to prevent the health effects induced by PM 2.5 .

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“…A general scheme of methyl radical formation and dCyd methylation under oxidative stress conditions is shown in Fig. 15 [ 67 , 68 ]. Endogenous compounds such as MetO, induced by smoking, inflammation and aging, can generate methyl radicals under oxidative stress conditions.…”

Section: Introductionmentioning

confidence: 99%

What causes human cancer? Approaches from the chemistry of DNA damage

Kasai

2016

Genes and Environ

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To prevent human cancers, environmental mutagens must be identified. A common mechanism of carcinogenesis is DNA damage, and thus it is quite possible that environmental mutagens can be trapped as adducts by DNA components. It is also important to identify new types of DNA damaging reactions and clarify their mechanisms. In this paper, I will provide typical examples of our efforts to identify DNA damage by environmental agents, from chemistry-based studies. 1) Oxidative DNA damage: 8-Hydroxydeoxyguanosine (8-OHdG, 8-oxodG) was discovered during a structural study of DNA modifications caused in vitro by heating glucose, which was used as a model of cooked foods. We found that various oxygen radical-forming agents induced the formation of 8-OHdG in DNA, in vitro and in vivo. Analyses of the urinary 8-OHdG levels are useful to assess the extent of oxidative DNA damage in a human population. 2) Lipid peroxide-derived DNA adducts: We searched for mutagens that react with deoxynucleosides, in model systems of lipid peroxidation. The reaction mixtures were analyzed by high performance liquid chromatography (HPLC), and we discovered various lipid peroxide-derived mutagens, including new mutagens. Some of these adducts were detected in human DNA. These mutagens may be involved in lipid peroxide-related cancers. 3) Methylation of cytosine by free radicals: Methylation of the cytosine C-5 position is an important mechanism of carcinogenesis, in addition to gene mutations. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred by a free radical mechanism. The possible role of this radical-induced DNA methylation in carcinogenesis will be discussed, in relation to the presently accepted concept of cancer epigenetics. In these studies, chemical analyses of the adducts formed in model reactions led to the discoveries of new mutagens and important types of DNA modifications, which seem to be involved in human carcinogenesis.

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Free radical-mediated cytosine C-5 methylation triggers epigenetic changes during carcinogenesis

Cited by 4 publications

References 49 publications

Tissue aging: the integration of collective and variant responses of cells to entropic forces over time

Tissue aging: the integration of collective and variant responses of cells to entropic forces over time

Vitamin B complex blocks the dust fall PM₂_.5‐induced acute lung injury through DNA methylation in rats

What causes human cancer? Approaches from the chemistry of DNA damage

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Free radical-mediated cytosine C-5 methylation triggers epigenetic changes during carcinogenesis

Cited by 4 publications

References 49 publications

Tissue aging: the integration of collective and variant responses of cells to entropic forces over time

Tissue aging: the integration of collective and variant responses of cells to entropic forces over time

Vitamin B complex blocks the dust fall PM2.5‐induced acute lung injury through DNA methylation in rats

What causes human cancer? Approaches from the chemistry of DNA damage

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Product

Resources

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Vitamin B complex blocks the dust fall PM₂_.5‐induced acute lung injury through DNA methylation in rats