Glutathione Transferases and the Multidrug Resistance - Associated Protein in Prevention of Potentially Carcinogenic Oxidant Stress in Breast Cancer
Abstract
4 HYDROXY 2 NONENAL IS A HIGHLY REACTIVE ALDEHYDE BYPRODUCT OF LIPID PEROXIDATION AND IS KNOWN TO BE HIGHLY CYTOTOXIC, DAMAGING BOTH DNA and protein. HNE has a unique structure which includes a lipid tail, and a polar head with an Cl aldehyde, a C3-C4 trans double bond, and a C4 hydroxy. By using compounds analogous in structure to HNE but lacking one individual component we have examined the contribution of each structural feature to the overall toxicity of the compound and determined the rank order as; aldehyde>trans double bond hydroxy. The length of the lipid tail is also important to the toxicity. These studies were done using growth inhibition and apoptosis induction as endpoints. We have also examined the mechanism of HNE induced apoptosis and found that HNE induces a p53 independent apoptosis in RAW 264.7 mouse macrophage cells. Using RAW cells expressing anti-apoptotic protein BCL2 we have also found the HNE induced apoptosis is cytochrome c dependent. These studies not only contribute to the knowledge of HNE toxicity but also present a possible link between oxidant stress induced lipid peroxidation and oxidant stress induced apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA384241
Entities
People
- Alan Townsend
- Robin Haynes
Organizations
- Wake Forest School of Medicine