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. 2014 Apr;8(4):SC01-3.
doi: 10.7860/JCDR/2014/8177.4233. Epub 2014 Apr 15.

Hypoxia induced DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart

Affiliations

Hypoxia induced DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart

Vidya G et al. J Clin Diagn Res. 2014 Apr.

Abstract

Background and aim: In Congenital Heart Disease (CHD), shunting of blood occurs through the anatomical defects which lead to mixing of oxygenated and deoxygenated blood. Chronic hypoxia which occurs due to the above said mechanism has the potency to cause DNA damage in children with CHD. In chronic hypoxia, there is a liberation of Reactive Oxygen Species (ROS) due to tissue injury as a result of ischemia and induction of hypoxia inducible factor - 1HIF-1 and p53 which in turn activates pro-apoptotic factors leading to alteration in the regulation of pro-apoptotic gene Blc-2 to be involved in causing the DNA damage. The extent of chronic hypoxia and the DNA damage depends on the nature of the anatomical heart defect. Hence, the present case-control study was conducted to find out the DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart and to compare the same.

Materials and methods: The study group was categorized into those with isolated septal defects and septal defects associated with great vessel anomaly based on echo-cardiogram. Age and sex matched healthy children were taken as controls. Single-cell gel electrophoresis - Comet Assay of Alkaline Version was performed conventionally and the comets were analyzed using comet score software.

Results and conclusion: The comet metrics was found to be statistically significant in children with isolated septal defect and septal defect with great vessel anomaly when compared with that of the controls. In addition, comet metrics also showed significantly increased DNA damage among children with septal defects associated with great vessel anomaly when compared to isolated septal defects. The data strongly suggests a linear correlation of severity of the anomaly involved with the degree of DNA damage as evidenced by lesser extent of DNA damage in isolated septal defect and greater in septal defect with great vessel anomaly.

Keywords: Comet Assay; DNA damage; Isolated Septal Defect of heart (ISD); Reactive Oxygen Species (ROS) and Hypoxia Inducible Factor – 1 (HIF 1); Septal Defect with Great Vessel Anomaly (SD with GVA).

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Figures

[Table/Fig-1a]:
[Table/Fig-1a]:
2D color Doppler showing VSD (Isolated Septal Defect) with left to right shunt
[Table/Fig-1b]:
[Table/Fig-1b]:
Schematic representation of 2D color Doppler showing VSD with left to right shunt LA – Left Atrium, RV – Right Ventricle, LV – Left Ventricle, VSD – Ventricular Septal Defect, IVS – Inter Ventricular Septum
[Table/Fig-2a]:
[Table/Fig-2a]:
Parasternal long axis view 2D Color Doppler showing VSD and Aortic Override (Septal Defect with Great Vessel Anomaly)
[Table/Fig-2b]:
[Table/Fig-2b]:
Schematic representation of Parasternal long axis view 2D Color Doppler showing VSD and Aortic Override LA – Left Atrium, RV – Right Ventricle, LV – Left Ventricle, VSD – Ventricular Septal Defect, MV – Mitral Valve, IVS – Inter Ventricular Septum,, AV – Aortic Valve
[Table/Fig-3]:
[Table/Fig-3]:
Comets - Controls
[Table/Fig-4]:
[Table/Fig-4]:
Comets – Isolated Septal Defect
[Table/Fig-5]:
[Table/Fig-5]:
Comets – Septal Defect with Great Vessel Anomaly Black arrow heads – comet head, Black arrows – comet tail

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