Xenobiotic Modulation of Human Mammary Epithelial Cell Gap Junctional Intercellular Communication and Growth

摘要

Man-made chemicals such as pesticides, polychlorinated biphenyls (PCBs), phthalate esters, and dioxin have been implicated in the etiology of breast cancer. Many xenobiotics such as DDT and PCBs have weak estrogenic activity and may enhance breast cancer formation by an estrogenic effect on breast epithelial cell growth. These agents also inhibit gap junctional intercellular communication (GJIC). This inhibition may contribute to the enhancement of breast epithelial growth and breast cancer formation by xenobiotics. The studies of this project have investigated the link between xenobiotic inhibition of human mammary epithelial cell GJIC, growth, and estrogenicity. These studies are highly relevant to the prevention of breast cancer. An understanding of the relationship between xenobiotic inhibition of GJIC, estrogenic activity, and the enhancement of growth in human breast epithelial cells will lead to more widely acceptable, mechanism-based arguments that xenobiotics are involved in the etiology of human breast cancer. This should lead to more focused regulatory efforts to reduce exposure to these agents.