CDC has ranked kidney cancer as the 7^th leading cause of cancer mortality in 2004 and surprisingly NCI estimated new cases and deaths from kidney cancer could be 54, 390 and 13,010 respectively in 2008 alone. Prime factors that precipitate this scenario include air and water pollution, food-borne toxic exposures, malnutrition, and lack of exercise. Constant encounters to toxic end products for clearance makes the kidneys extremely vulnerable to toxic/carcinogenic changes. Although kidney's complex anatomy is built to handle such consequences, a significant drop in tissue antioxidant levels can potentially navigate the cells to a wrong path. In this context, antioxidants appear to be instrumental in cellular defense mechanisms, and numerous publications attest to the fact that diets rich in antioxidant phytochemicals could potentially prevent cancer. Therefore, this study explored whether continuous exposure to a powerful antioxidant (proanthocyanidin mixture: PM) would reduce nephrocarcinogenic potential of DMN. Animals were divided into four groups (GrI: Control; GrII: PM alone; GrIII: DMN alone; GrIV: DMN+PM). Gr-I and Gr-III were on control diet, whereas Gr-II and Gr-IV were on PM-diet. In order to initiate kidney cancer, Gr-III and Gr-IV received DMN (5 mg/kg for 0-8 weeks; 10 mg/kg for 4 weeks, ip) between 0-3 months. Animals were sacrificed every 3 months for serum chemistry and evaluation of carcinogenic changes in the kidneys. Microscopic evaluation revealed DMN-induced orderly neoplastic changes and presence of nuclei of diverse morphology (apoptotic, necrotic and apocrotic). Co-exposure to PM along with DMN reduced animal mortality and carcinogenic changes in the kidneys. Minor changes in BUN/creatinine levels and genomic DNA fragmentation (less than 2-fold increase at 3, 6, 9 & 12mos) were observed. These results suggest that long term co-exposure of a proanthocyanidin mixture may be extremely beneficial in reducing, delaying and/or counteracting DMN-induced nephrocarcinogenesis.