Mechanisms of PCBS-Induced Breast Cancer
Annual rept. 1 Sep 1998-31 Aug 1999
KENTUCKY UNIV LEXINGTON
Pagination or Media Count:
For understanding the possible role of PCBs in breast cancer induction we have to 1. Unravel the mechanisms of PCB carcinogenesis 2. Investigate whether these mechanisms occur in the breast. We found that i. 4-chlorobiphenyl is an initiator in rat liver ii. Human breast tissue is qualitatively able to metabolically activate PCBs similarly as the liver iii. in mouse liver PCBs are activated to metabolites that bind to nuclear protein and DNA the structure of the adduct still needs to be determined iv. PCB quinone and hydroquinone metabolites bind to DNA in vitro, deplete intracellular glutathione and produce reactive oxygen species ROS in cells in culture v. PCB treatment results in the activation of transcription factors, 8-OH-dG formation, and increase in lipid peroxidation derived endogenous polar DNA adducts in rat liver vi. PCBs produce oxidative stress by redox reactions of the metabolites orand by changes in the levels of anti-oxidant enzymes and cofactors vii. Human breast tissue varies greatly in proanti-oxidant enzyme activity. Oxidative stress could be the major factor in PCB carcinogenesis. Therefore we will analyze oxidative stress in breast tissue after PCB treatment, and try to identify enzymatic risk factors for PCB carcinogenesis in women.
- Anatomy and Physiology
- Medicine and Medical Research