title: Hypoxia induced DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Junior Resident, Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research , Puducherry, India .
authors: Vidya
authors: V
authors: G
authors: Associate Professor, Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research , Puducherry, India .
authors: Suma
authors: S
authors: H Y
authors: Professor and Head, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research , Puducherry, India .
authors: Vishnu
authors: V
authors: Bhat B
authors: Professor and Head, Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research , Puducherry, India .
authors: Parkash
authors: P
authors: Chand
authors: Senior Professor, Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research , Puducherry, India .
authors: Ramachandra
authors: R
authors: Rao K
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)