Patricia D. Durant, PhD
Academic Tutor at Wake Forest University
Adjunct Professor at Forsyth Technical Community College
Molecular Medicine and Translational Sciene, PhD, 2004-2010
Wake Forest University School of Medicine
BS (Biology with Chemistry minor), 1995, Winston-Salem State University
Genetic damage, which can result in changes in function, is believed to lead to a wide range of diseases, including cancer. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, can cause genetic damage. Human exposure to B[a]P occurs primarily through the smoking of tobacco, but can also come from inhalation of polluted air by automobile exhaust fumes, second-hand cigarette smoke, and ingestion of charbroiled foods and water contaminated by combustion effluents. Once inside of a cell, B[a]P undergoes metabolism to reactive electrophiles capable of binding covalently to DNA. This is what can lead to genetic damage, resulting in changes in function, and possibly cancer.
Our laboratory has developed bifunctional transgenic cell lines to study the dynamic competition between metabolic activation and detoxification. Our novel system engineers stably transfected cell lines expressing the appropriate Phase I (i.e. CYP450) and Phase II (i.e. GST) isozymes. This model allows us to look at the metabolic actions of P450 activation and GST conjugation together in a cellular context, and in the presence of the parent compound and its metabolites. This model is compared to prior experiments that have primarily been with crude or purified GST preparations, often with extracellular activation using a microsomal preparation.
My area of interest is investigating agents that are classified as chemopreventive (i.e., isothiocyantes, resveratrol, genistein, curcumin, and galangin, to name a few). Two potential mechanisms of chemoprevention are inhibiting activation of parent compounds to their more genotoxic or cytotoxic metabolites, or enhancing detoxification after activation. The dynamic competition between these two metabolic steps has even greater significance. Agents that selectively inhibit Phase I enzymes, or preferentially activate Phase II more than Phase I enzymes would likely have the most promise in chemoprevention. Understanding just how these agents affect the dynamics of competition between activation and detoxification of potent carcinogens such as B[a]P will offer a clearer picture of how they can be used to reduce carcinogenic genetic damage in humans.
Honors and Awards:
Awarded Grant Supplement Number: 3R01ES010175 - 06S1, PI Name: TOWNSEND, ALAN J, July 2006 – December 2009.
Recipient - WFSM Institutional Graduate Teaching Assistantship, August 2004 – June 2006.
Recipient - Love, Incentive, and Centennial Scholarships, 1991 – 1995, Winston-Salem State University.
Dean’s List, 6 semesters out of 8, 1991 – 1995.
Durant PD, Leone-Kabler S, Scott LM, Townsend AJ. Inhibition by Chemopreventive Agents of hCYP1A1 and hCYP1B1 Activation of Benzo[a]Pyrene (B[a]P) and B[a]P(-)7,8-diol (BPD) to Toxic and Mutagenic Metabolites, Wake Forest University Graduate School Forum, April 2009.
Durant PD, Leone-Kabler S, Scott LM, Townsend AJ. Inhibition by Chemopreventive Agents of hCYP1A1 and hCYP1B1 Activation of Benzo[a]Pyrene (B[a]P) and B[a]P(-)7,8-diol (BPD) to Toxic and Mutagenic Metabolites, American Chemical Society (ACS) Meeting, March 2009.
Scott LM, Durant P, Leone-Kabler S, Wood CE, Register TC, Townsend A, Cline JM (2008) Effects of prior oral contraceptive use and soy isoflavavonoids on estrogen-metabolizing cytochrome P450 enzymes. Journal of Steroid Biochemistry and Molecular Biology, 112, 179-185.