Kristina Kraakmo, '09
Ph.D. in Applied Mathematics
Development of a Quantitative Model to Predict Tumor Incidence in Mice and Rats Conducted at North Carolina State University as part of the NSF Research Experience for Undergraduates in Mathematics program, Summer 2009. Mentors: Dr. N.S. Luke, and Dr. H.A. El-Masri USEPA/ORD/NHEERL/ETD/PKB, Research Triangle Park, NC Participants: Madison Brandon, Kristina Kraakmo & Kristy Mitchell Abstract: Biologically-Based Dose Response (BBDR) modeling of environmental pollutants can be utilized to inform the mode of action (MOA) by which compounds elicit adverse health effects. Chemicals that produce tumors are typically described as either genotoxic or non-genotoxic. One commonly proposed MOA for non-genotoxic carcinogens is characterized by the key events of cytotoxicity and regenerative proliferation. The increased division rate associated with such proliferation causes an increase in the probability of mutations, which can result in tumor formation. In this project, three carcinogens that are thought to induce tumors in mice through a cytotoxic mode of action (chloroform, carbon tetrachloride, and dimethyl formamide) will be quantitatively compared using a generalized BBDR quantitative model for tumor incidences. For each compound, a physiologically based pharmacokinetic (PBPK) model will be developed and linked to a pharmacodynamic model of cytolethality and cellular proliferation. The rate of proliferation is then linked to a clonal growth model which predicts tumor incidences. The BBDR model will be used to quantitatively indentify limits of cellular injury and proliferation that would result in a significant increase in tumor incidences in mice. Additionally, the BBDR model will be applied to investigate the impact of species differences in tumor incidences between rats and mice.
Summer Research Institution
North Carolina State University
Applied Mathematics | Mathematics
Kraakmo, Kristina, "Kristina Kraakmo, '09" (2017). McNair Scholars. 68.