Epigenetic effects

These inhibitors act directly on the enzyme without the necessity for incorporation into the DNA. In theory, this should shift the dual activity of reactivation of silenced genes and cytotoxicity towards the epigenetic effects which may result in reduced side-effects. But the proof for that remains yet to be established. 

The inhibitors available for human use, azacitidine and decitabine, have been approved for the treatment of myelodysplastic syndrome (MDS) [98, 99[. MDS summarizes a set of different conditions that affect the maturation of blood cells. It is a group of bone marrow stem cell malignancies that have a pathogenetic overlap with acute myeloid leukemia, show peripheral blood cytopenias and, in more advanced subtypes, varied degrees of maturation arrest [100]. Both drugs are approved for all subtypes of MDS. Response rates are usually around 30%. The question whether the clinical benefit results more from epigenetic effects and re-activation of silenced maturation factors or more from cytotoxic effects on the immature hyperproliferative cells remains open. 

Henikoff S, Matzke MA. Exploring and explaining epigenetic effects. Trends Genet 1997 13 293-295. 

In real life , humans and animals can be exposed to some toxicants both pre- and postnatally. Many organic xenobiotics have the potential to bioaccumulate within exposed individuals, possibly affecting future generations by way of genetic and epigenetic effects. However, reproductive endpoints, such as conception rates and sperm counts, are relatively insensitive, and subtle, toxicant-induced changes in reproductive efficiency can be overlooked or missed (Evans, 2007). 

Finally, a third approach has been proposed with five stages that focus on the chemical structure, DNA-reactivity, epigenetic effects, limited bioassays, and finally, the application of accelerated bioassays. These accelerated bio assays require 40 weeks and apply to the use of sensitive markers for induction of neoplasia in comparison to positive control compounds for important organs in human carcinogenesis. It enables data acquisition of the entire carcinogenesis process directed toward developing mechanistic information. This system would have the potential to replace the chronic bioassay in rodents in some circumstances and could serve a analternative to a chronic bioassay in a second species. ... 

Stoccoro A, Karlsson HL, Coppede F, Migliore L (2013) Epigenetic effects of nanosized materials. Toxicology 313(1) 3—14. 

Dorner, G., Gotz, F., Rohde, W., Plagemann, A., Lindner, R., Peters, H., Ghanaati, Z. (2001). Genetic and epigenetic effects on sexual brain organization mediated by sex hormones. Neuro. Endocrinol. Lett. 22 403—409. 

Contag, B. Epigenetic effectiveness of complete carcinogens specific interactions of polycyclic aromatic hydrocarbons and aminoazo dyes with cholesterol and apohpoprotein A-I. Z Natuiforsch., C J. Biosci. 2005, 60, 799-806. 

Tumorigenidty The epigenetic effects of arsenic in relation to carcinogenesis have been reviewed, including its effects on DNA meth-ylation, global DNA hypomethylation, gene promoter methylation, histone acetylation, histone methylation, histone phosphorylation, and miRNA expression [32 ]. 

Epigenetic, 2404, 2834 Epigenetic effects, 2401 Epiisopiloturine, 877 8- pi-kingiside, 3029, 3041 Epilachna paenulata, 4095 Epilepsy, 877, 3644, 3966 Epileptic seizures, 1208... 

Cenotoxicity DNA damage, and apoptosis mutagenicity, clastogenicity, epigenetic effects... 

Respiratory Data from experimental animals suggest that folic acid given to the mother during pregnancy may be associated with an increased risk of asthma in the offspring by an epigenetic effect involving altered DNA methylation [28 ]. 

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