Underorganisation of chromatin structure in human metaphase chromosomes by induction of 5-aza-2'-deoxycytidine (Decitabine) [Baz analogu 5-aza-2'-deoksisitidin (Desitabin) in insan kromozomlarinda neden oldugu kromatin organizasyon bozukluklari]

Abstract

Human metaphase chromosomes were exposed to different concentrations (10-8-10-2 M) of 5-aza-2'-deoxycytidine, a DNA methyl inhibitor, in order to determine the in vivo effect of the agent on chromosome packaging. It has been found that the agent was substituted with cystosine in the newly synthesised DNA strand and it distrupted the chromosome condensation. GTG and C banding techniques revealed that the agent caused demethylation in DNA regions that were substituted with cytosine. In the DNA regions that hypomethylation was evident, chromosomes could not complete their normal condensations and remained in under or decondensated form. On the other hand the agent caused significant alterations in chromosome structure associated with different dosages and duration. Despite its effect on decondensation, the agent also caused the deconfiguration (24 hours), segmantation, increased juxtacentomeric-telomeric associations, gaps, fragility, chromatid and isochromatid breaks and pulverisation in the chromosome structure. According to the present findings, it could be suggested that the DNA methylation is an important mechanism in chromosome packaging and organisation. Alterations that are established in methylation patterns may cause significant structural abnormalities in human chromosomes.