Glutathione Transferases and the Multidrug Resistance - Associated Protein in Prevention of Potentially Carcinogenic Oxidant Stress in Breast Cancer

摘要

Oxidative stress has been implicated as a causative or contributory factor in breast cancer. Lipid peroxidation is one result of oxidative stress, and may be common in breast tissue due to the high fat content. A highly reactive aldehyde byproduct of lipid peroxidation, 4 hydroxy-2-nonenal (HNE) is known to damage both DNA and protein. We have determined the structural components that are most critical for HNE toxicity, using compounds analogous in structure to HNE but lacking 5 specific structural features. With growth inhibition and apoptosis induction as endpoints, the rank order of importance was aldehyde>trans double bond>4hydroxyl. Longer lipid chains also yielded greater toxicity than shorter.