Makenzie Cavil

Furan is a compound found in the environment, commercial food products, and tobacco smoke that has been shown to induce hepatocyte proliferation, cyto-lethality, and cancer in animal models. For these reasons, furan is a potential human carcinogen. Furan induces its carcinogenic effects through metabolic breakdown into reactive dialdehyde, cis-2-butene-1,4-dial (BDA). BDA can further react with glutathione (GSH) in the liver, to form GSH-BDA, which has been shown to crosslink with endogenous amines to form protein and DNA adducts. Previous work identified an unknown hepatocyte metabolite with a molecular weight consistent to GSH-BDA-glycerolphosphorylethanolamine (GPE). GPE is a primary amine-containing phospholipid prevalent in the phospholipid bilayer. The presence of GSH-BDA-GPE in hepatocytes suggests that its downstream metabolite NAC-BDA-GPE may be present in urine. To evaluate the reactivity of GPE, de-acylated soy lecithin was used as a source of GPE and reacted with GSH or NAC, and BDA. Reaction products were purified by HPLC with UV detection. Mass spectrometric analysis of purified NAC-BDA-GPE and GSH-BDA-GPE peaks confirmed the presence of ions with masses of 426 and 571 g/mol respectively, consistent with their predicted structures. NMR analysis of NAC-BDA-GPE further supports its structure. However, the GSH-BDA-GPE reaction product was too unstable under the purification conditions to obtain NMR data. Future work will focus on optimizing the GSH-BDA-GPE HPLC purification method to complete its characterization. Our initial results support the hypothesis that the furan-derived reactive metabolite BDA may form crosslinks with glycerolphosphorylethanolamine in the liver membrane.