ALTERATION OF NUCLEOTIDE EXCISION REPAIR BY AQUATIC ESTROGENS: IMPLICATIONS FOR CARCINOGENESIS

ALTERATION OF NUCLEOTIDE EXCISION REPAIR BY AQUATIC ESTROGENS: IMPLICATIONS FOR CARCINOGENESIS

By: Emily Glynn Notch
Thesis Advisor: Dr. Greg Mayer
A Lay Abstract of the Thesis Presented
In Partial Fulfillment of the Requirements for the
Degree of Doctor of Philosophy
(in Biochemistry and Molecular Biology)
May, 2010

The use of pharmaceuticals by humans has resulted in these compounds becoming common aquatic contaminants. In particular, pharmaceutical hormones (e.g. oral contraceptives) have profound impacts on aquatic organisms after entering waterways via wastewater treatment plants. Understanding the impacts such compounds have on fish and other aquatic organisms is important for mitigating environmental impacts as well as understanding their implications in human health disparities. Estrogens are known carcinogens but current science lacks a complete understanding of estrogen-induced cancer. In addition to reproductive effects, synthetic estrogens have the potential to alter DNA repair in exposed aquatic organisms at environmentally relevant concentrations. This alteration of DNA repair results in higher amounts of DNA damage in fish coexposed to  synthetic estrogens and DNA damaging agents. In addition to laboratory exposures, fish exposed to wastewater treatment effluent from different treatment plants in northern Maine also show altered DNA repair processes. This alteration of DNA repair may result in higher incidence of DNA  mutations and tumors in exposed fish. This research also has implications for human health by uncovering new mechanisms for estrogen mediated  cancers.