Glutathione Transferases and the Multidrug Resistance - Associated Protein in Prevention of Potentially Carcinogenic Oxidant Stress in Breast Cancer
Abstract
The purpose of this project is to determine: a) mechanisms of toxicity or DNA damage by 4-hydroxy-nonenal (FINE), an oxidative stress-induced lipid aldehyde, and b) the protective functions of several key cellular enzymes against FINE and other potentially carcinogenic redox-active electrophiles. The focus is on the application of transgenic cell lines that express specific protective genes. The findings to date are: 1) the most efficient GST isozyme tested does not confer resistance to HNE; 2) GST and MRP do not cooperate to provide resistance to HNE or to tBuOOH; 3) the toxicity of HNE is mediated primarily via apoptosis; 4) the aldehyde function is required for FINE toxicity; 5) toxicity and apoptosis, and covalent modification of proteins by FINE can be completely blocked by transfected human aldehyde dehydrogenase-3; 6) the C2=C3 double bond also makes an important contribution to FINE reactivity, but is less critical than the -CHO; 7) increasing chain length enhances toxicity of FINE (least impact); 8) expression of the antioxidant gene Bcl-2 also protects against apoptosis by FINE.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADA381152
Entities
People
- Robin L. Haynes
Organizations
- Wake Forest School of Medicine