Fellows Project Report Student Name : Zachary Foulks Project Title : Analysis of Pteridines in Isogenic Breast Cancer Model

The biosynthetic pathways responsible for elevated concentrations of pteridine derivatives in urine samples of women with breast cancer are not well understood. This study aimed to characterize pteridine levels and related metabolic rates in a progressive breast cancer cell line model that included the following lineages: MCF10A (non-cancerous), MCF 10AT (premalignant), and MCF10CA1a (metastatic). Pteridine derivatives were quantified using a previously developed high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) workflow alongside a newly developed pteridine extraction protocol that together enabled rapid and sensitive quantification. Intracellular and extracellular pteridine levels were compared across progressive stages of the cell lineages with folic acid and guanosine triphosphate (GTP) precursor dosing. Most of the cellularly-created pteridines either remained in the extracellular space or were extracellularly transported. Additionally, the pattern of pteridine production suggests possible cancer-induced changes that can be monitored in future breast cancer diagnostic procedures using only urine samples. We are preparing a manuscript for publication.