While bacteria are the etiologic factors common to all inflammatory periodontal diseases (IPD), it is recognized that host response influences the severity and extent of periodontal destruction. Diabetes accentuates this and gingival healing is more difficult to achieve in such periodontal patients. It is not known what molecular lesions are responsible for the pathogenesis of chronic inflammatory periodontal disease. We propose that DNA repair capability of cells in the chronically inflamed gingiva is depressed. It is logical to assume that diseased gingiva are constantly exposed to inflammation-mediated superoxide and other bactericidal agents that inflict cellular DNA damage which demands a proficient DNA repair. Accumulation of such sublethal DNA damage over a period, reflects in altered cell behavior and faulty expression of certain genes including those of collagen, the principal connective tissue protein. Our studies to date support this idea. We have observed that chronically inflamed gingiva obtained from patient with advanced periodontitis possessed greatly reduced activity of poly(ADP- ribose) synthetase which synthesizes poly(ADP-ribose), an obligatory regulator of DNA repair. In addition, cultured fibroblasts from diseased gingiva exhibited a diminished potential for defense against superoxide, and consequently, may undergo a greater relative DNA damage. We propose to study whether defects related to DNA damage- repair are also associated with gingivitis. The longterm objective of our proposal is to delineate biochemical lesions in IPD. We seek to evaluate our ideas by studying defense potential against DNA damage, liposome-dependent endocytosis, DNA damage and repair, in cultured fibroblasts and macrophages and also collagen synthesis in fibroblasts derived from gingival biopsies from patients with gingivitis, periodontitis and from periodontal patients with diabetes. The results of our studies are expected to define gingivitis and periodontitis in terms of molecular lesions affecting cellular functions in these diseases. In addition, our studies may explain the severity of periodontal destruction associated with diabetes.
