5-hydroxymethylfurfural and Precancerous-Conditions

5-Hydroxymethylfurfural (5-HMF) as a product of the Maillard reaction is found in many foods. Estimated intakes range between 4 and 30  mg per person and day, while an intake of up to 350  mg can result from, e.g., beverages made from dried plums. In vitro genotoxicity was positive when the metabolic preconditions for the formation of the reactive metabolite 5-sulphoxymethylfurfural were met. However, so far in vivo genotoxicity was negative. Results obtained in short-term model studies for 5-HMF on the induction of neoplastic changes in the intestinal tract were negative or cannot be reliably interpreted as "carcinogenic". In the only long-term carcinogenicity study in rats and mice no tumours or their precursory stages were induced by 5-HMF aside from liver adenomas in female mice, the relevance of which must be viewed as doubtful. Hence, no relevance for humans concerning carcinogenic and genotoxic effects can be derived. The remaining toxic potential is rather low. Various animal experiments reveal that no adverse effect levels are in the range of 80-100  mg/kg body weight and day. Safety margins are generally sufficient. However, 5-HMF exposure resulting from caramel colours used as food additives should be further evaluated.

Topics: Animals; Beverages; Colonic Neoplasms; Flavoring Agents; Food Additives; Food Analysis; Furaldehyde; Humans; Mice; Mutagenicity Tests; Precancerous Conditions; Rats; Risk Assessment

5-Hydroxymethylfurfural (HMF) is produced in large quantities during the processing of food containing carbohydrates and can be metabolised to 5-sulfooxymethylfurfural (SMF), a reactive intermediate that can bind to DNA and cause mutagenic effects.. Three to six days after birth, multiple intestinal neoplasia (Min/+) mice were given a single subcutaneous injection of either 500 mg/kg body weight (bw) HMF, 25 mg/kg bw SMF or vehicle (0.9 % NaCl), and were euthanised at 12 weeks of age. The number and size of adenomas and flat aberrant crypt foci (ACF) were counted in the intestine.. HMF increased the number of small intestinal adenomas (p=0.033), whereas SMF increased the flat ACF number in the large intestine (p=0.025). Treatment with HMF and SMF had no effect on the size of the adenomas.. These results show that both HMF and SMF are weak intestinal carcinogens in Min/+ mice.

Topics: Adenoma; Adenomatous Polyposis Coli Protein; Animals; Carcinogens; Female; Furaldehyde; Intestinal Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Necrosis; Precancerous Conditions

We have previously shown that thermolyzed sucrose in the diet promotes the growth of aberrant crypt foci (ACF) in the rat. HPLC analysis of the light caramel colored product showed that it contained 1% 5-hydroxymethyl-2-furaldehyde (HMF), confirmed by mass and NMR spectroscopy. To determine whether HMF was responsible for the promotion of ACF by thermolyzed sucrose, 45 F344 female rats were initiated with the colon carcinogen azoxymethane (AOM), and a week later were randomized to four groups receiving AIN-76 diets containing untreated sucrose, 20% thermolyzed sucrose, 20% butanol extracted thermolyzed sucrose (HMF free) or 1% HMF. Thermolyzed sucrose in the diet led to larger ACF as previously observed. Thermolyzed sucrose extracted to remove HMF, did not affect ACF size, but 1% HMF added to the diet led to a larger ACF both with relation to average size and number of ACF of larger sizes (P < 0.05). To determine whether HMF had initiating effects, 172 female F344 rats were given water, HMF (at doses to 300 mg/kg) or AOM (5 mg/kg) by gavage twice and the total number of ACF was scored 30 days later. The results demonstrated that HMF induces ACF in a dose-dependent manner (P < 0.02), though the effect was much weaker than that of AOM. We conclude that sugar heated under household cooking conditions may act as both an initiator and a promoter of colon cancer because of the presence of HMF.

Topics: Animals; Azoxymethane; Colon; Colonic Neoplasms; Female; Furaldehyde; Hot Temperature; Precancerous Conditions; Rats; Rats, Inbred F344; Sucrose