Thermolysis of carbohydrates and intestinal cancer risk.

Increased colorectal cancer risk is associated with a Western style diet and several carcinogenic and hazardous compounds are formed during heat processing. Acrylamide is formed in µg/amounts during heating of sugar-rich foods, but 5-hydroxymethylfurfural (HMF) is produced in much larger quantities, with levels exceeding 1 g/kg in several food items. HMF can be metabolically activated by sulfotransferases to a highly reactive derivative that binds to DNA, but has barely been studied with respect to potent ial adverse effects. Sulfotransferases show higher expression in human intestine than in mouse intestine, complicating assessments of human health risk from HMF exposure in conventional animal studies. The aim of the project is to investigate the human ex posure to the thermolysed sugar product hydroxymethylfurfural (HMF) and whether this exposure may constitute a risk for human intestinal cancer. We will assess human HMF-exposure by using food intake data and biomarkers of exposure and perform experiments with HMF and metabolites in novel humanised transgenic mouse models (expressing human intestinal sulfotransferases) for intestinal carcinogenesis. We will measure mutation frequencies after HMF exposure and characterise the mutations. The project will be carried out in close collaboration with scientists in Austria, Germany and Denmark. The project will provide novel knowledge on the human HMF exposure and whether this exposure would constitute a human intestinal cancer risk. Furthermore, the project wil l reveal whether humans are more sensitive to potential intestinal carcinogens bio-activated by sulfotransferases than mice; information that would be crucial in future risk assessments. The project will also provide information on which mutations that ca n be expected from HMF exposure. Finally, this research project will provide education of a master student and a PhD student in toxicology and give both experiences in international scientific collaboration.