Investigation of furan metabolite BDApolyamine crosslinks in cell toxicity and carcinogenesis

Abstract

Furan is a product of incomplete combustion present in canned foods, tobacco smoke and exhaust fumes. It has been shown to be a liver toxicant and carcinogen in rodents. This project seeks to determine the toxic carcinogenic effect of furan in human liver cells as these remains unknown. Cis-2-butene-1,4-dial (BDA), a highly reactive breakdown product of furan, has been shown to form stable crosslinks with polyamines and glutathione in vivo and in cell models. The spermine and ornithine crosslinks were synthesized and purified using high pressure liquid chromatography and characterized using mass spectrometry and nuclear magnetic resonance. The synthesized crosslinks will be introduced into human liver cell cultures to study if these products of furan metabolism play a role in liver toxicity and carcinogenicity. These data will be combined with others to determine if furan is a human health concern.