The Crucial Role of Genotyping CYP2A6 and CYP1A2 Enzymes in Understanding the Metabolism of PCBs

• Applicant: Dr. Nergis Selma Aslan, Ph.D.
• Subject Area: Toxicology, Laboratory Medicine
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561565548

Polychlorinated biphenyls (PCBs) are synthetic industrial chemicals that persist in the environmentand pose significant health risks to humans. The risks associated with this include cancer, endocrine disruption, and impairment of the immune system. The metabolism of PCBs in humans is primarily mediated by cytochrome P450 (CYP) enzymes, specifically CYP2A6 and CYP1A2. These enzymes transform PCBs into metabolites, which may either be less toxic or, in some cases, more harmful than the parent compound. The activity of these enzymes can vary significantly among individuals due to genetic polymorphisms, which may influence the metabolism, detoxification, and potential health risks associated with PCB exposure. The goal of this project is to study how genetic variations (polymorphisms) in the CYP2A6 and CYP1A2 enzymes affect PCB metabolism in humans. We will analyze DNA samples from 360 individuals with known PCB exposure levels to identify specific genetic variations in these enzymes. By comparing these variations with individual PCB metabolism rates and the levels of toxic byproducts, we hope to understand how genetic differences can impact susceptibility to PCB-related health risks, such as cancer. The study will use advanced genotyping techniques and statistical analysis to investigate the genetic factors affecting individual PCB metabolism differences. This research is crucial in understanding these genetic factors, which is important to improving personalized risk assessments for people exposed to PCBs, particularly those in areas with high PCB contamination. Additionally, this research will offer valuable insights into toxicokinetics and help develop more effective public health strategies to reduce the risks associated with persistent organic pollutants. This project will improve our understanding of individual differences in xenobiotic metabolism by elucidating the relationship between genetic variability and PCB metabolism. This will lead to more personalized interventions and preventive measures in environmental health.

• DFG Programme: WBP Position