Study of 5-hydroxymethylfurfural and its metabolite 5-sulfooxymethylfurfural on induction of colonic aberrant crypt foci in wild-type mice and transgenic mice expressing human sulfotransferases 1A1 and 1A2.

Scope: It was reported that the Maillard product 5-hydroxymethylfurfural (HMF) initiates and promotes aberrant crypt foci (ACF) in rat colon. We studied whether 5-sulfooxymethylfurfural (SMF), an electrophilic and mutagenic metabolite of HMF, is able to induce ACF in two murine models.

Methods And Results: In the first model, FVB/N mice received four intraperitoneal administrations of SMF (62.5 or 125 mg/kg) or azoxymethane (10 mg/kg). Animals were killed 4-40 weeks after the last treatment. A total of 1064 ACF and five adenocarcinomas were detected in the azoxymethane-treated groups (20 animals), but none in the negative control and SMF-treated groups (35 and 50 animals, respectively). In the second model, HMF was administered via drinking water to wild-type FVB/N mice and transgenic mice carrying several copies of human sulfotransferase (SULT) 1A1 and 1A2 genes. HMF SULT activity was clearly elevated in cytosolic fractions of colon mucosa, liver and kidney of transgenic animals compared to wild-type mice and humans. The animals (six per group) received 134 and 536 mg HMF/kg/day for 12 weeks. HMF did not induce any ACF either in wild-type or transgenic animals.

Conclusion: We found no evidence for an induction of ACF by HMF or its metabolite SMF in extensive studies in mice.