Chronic inflammatory periodontal disease (CIPD) is the major cause of tooth loss in adult human population. A common observation in CIPD, is that acute inflammation leads to predominantly chronic state in which the diseased gingiva does not usually heal. Although bacterial plaque has been recognized as its primary etiologic agent, the precise mechanisms involved in the disease process are not understood. Superoxide radical is an important product of inflammation and is known to cause fragmentation in cellular DNA. In CIPD through chronic and persistent exposure to superoxide radical, periodontal tissues undergo cellular changes as a result of single strand splits in the somatic chromosomes. Such cells have diminished functional capacity. Our proposal is based on the hypothesis that in CIPD, the damaged DNA is not repaired efficiently because of a defect in the synthesis of poly(ADP-ribose). Poly(ADP-ribose), a chromatin-bound polymer of ADP-ribose derived from NAD+, has been shown to be essential for DNA repair. Also, the synthesis of PADPR is stimulated in response to cellular DNA breaks. Results of our preliminary study provide support to the proposed mechanism. We observed a marked reduction in the activity of poly(ADP-ribose) synthetase suggesting a diminished capacity for poly(ADP-ribose) synthesis, in chronically diseased gingiva. The objective of our proposal is to investigate whether a defect in poly(ADP-ribose) synthesis leading presumably to an inefficient DNA repair, is involved in the mechanism of CIPD. We plan to study a) the status and capability of DNA repair and b) the synthesis of poly(ADP-ribose) and its chain lengths in healthy and diseased gingival tissues from CIPD patients and in gingival fibroblasts derived from these tissue samples. Our long-term objective is to establish a relation between failure to repair DNA and inability of chronically inflamed gingiva to heal. The results of our studies may lead to a better understanding of the mechanisms involved in CIPD.
