|
|
Molecular mechanisms of carcinogenic effects of alcohol
Vepřková, Jana ; Kábelová, Adéla (advisor) ; Novotná, Božena (referee)
Alcohol (ethanol) enters the human body mainly through ingestion of alcoholic beverages and its chronic consumption is considered a worldwide socio-economic problem. Besides others, alcohol consumption increases the risk of development of breast, liver, colorectal and upper aerodigestive tract cancer. In the liver, ethanol is metabolised into toxic acetaldehyde which is the main cause of DNA damage leading to cancer development. Acetaldehyde covalently interacts with nucleotides in the DNA forming DNA adducts such as N2 -ethylidene-2'-deoxyguanosine or S- and R-α-methyl-γ-hydroxy-1,N2 - propano-2′-deoxyguanosine. Acetaldehyde can also interact with proteins and disrupt their function. Ethanol metabolism by cytochrome P450 2E1 leads to production of reactive oxygen species, that subsequently damage cellular molecules such as lipides and DNA. Ethanol also initiates carcinogenesis through aberant DNA methylation or interference with retinoic acid metabolism. In cancer development, alcohol interacts with other environmental and genetic factors, which can increase the risk of developing cancer in predisposed individuals.
|
|
| |
|
|
Methylace histonu H3K9 v lidských krevních buňkách a v granulocytech pacientů s myeloidní leukemií
Lukášová, Emilie ; Falk, Martin ; Kořistek, Z. ; Kozubek, Stanislav ; Grigoryev, S. ; Kozubek, Michal ; Ondřej, Vladan ; Kroupová, I.
Common heterochromatin antigenic protein markers while present in human blood progenitor CD34+ cells, differentiated lymphocytes and monocytes are absent in neutrophile granulocytes and, to large extent, in eosinophiles. In acute CML and AML, strong methylation of H3K9 and all isoformes of HP1 are detected. In chronic forms of CML, no strong correlations among the level of histone methylation, disease progression and modality of treatment were observed. Reprogramming of leukemia HL60 cells to terminal differentiation by retinoic acid does not eliminate histone H3K9 methylation and the presence of HP1 isoformes from differentiated granulocytes. Our study shows for the firs time that histone H3 methylation may be dramatically changed during normal cell differentiation.
|
guest ::
