Project 1-Basic Science

William G. Nelson, M.D., Ph.D

Effects of CAM Interventions on Oxidative DNA
Damage in Cancer Cells

This project proposal embodies a plan to address mechanisms underlying the effects of CAM approaches to cancer. The hypothesis that CAM interventions can reduce oxidative stresses leading to oxidative genome damage in "oxidation tolerant" will be tested by:

1. assessing the contribution of host neuroendocrine stress to oxidative DNA damage in human breast and prostate cancer cells carrying defective alleles,
2. determining the effects of neuroendocrine stress on oxidative DNA damage in different organs in mice carrying disrupted alleles,
3. characterizing the effects of treatment on oxidative DNA damage in vivo in human prostate cancer cells,
4. evaluating the effects of treatment on oxidative DNA damage in mice with defects, and
5. exploring the effects of treatment on changes in gene expression in vivo in human prostate cancer cells.

Our focus will be on the effects of CAM interventions on the accumulation of pro-mutagenic oxidative genome damage in cells and tissues containing defective genes. To promote integration and coordination with other Johns Hopkins CAM Center Project proposals and core resources, we will direct our studies at preclinical models of prostate and breast cancer. Approximately 230 animals will be required for the various experiments.