Oxidative DNA damage is becoming increasingly implicated in late onset neurodegenerative diseases such as Alzheimer's, Parkinson's Amyotrophic lateral sclerosis (ALS) and in aging. A pathological feature of these diseases, and in aging, is the gradual loss of a subset of CNS neurons, possibly due to oxidative stress and free radical formation. Furthermore, evidence continues to accumulate implicating oxidative DNA damage and repair, or lack of repair, in cancer progression and development. The commercial availability of a panel of well-characterized, specific antibodies would enable researchers in these areas to more rapidly determine the significance of these enzymes in their field of interest. Specific aims during Phase I include: (1) Produce affinity purified polyclonal antibodies to the key enzymes in oxidative DNA damage repair. (2) Produce phosphospecific antibodies to the multifunctional APE/ref-1 protein, an enzyme that is involved in not only the repair of damaged DNA, but is the major redox factor of numerous onco-proteins (e.g., Fos, Jun, p53). (3) Characterize these antibodies in various cancer and disease tissues. In Phase II, expand the uses of these antibodies to determine the relationship between the expression (or lack thereof) of these repair enzymes and disease processes and determine the diagnostic and prognostic implications.
