5-hydroxymethylfurfural and Intestinal-Neoplasms

Humans express sulfotransferases (SULTs) of the SULT1A subfamily in many tissues, whilst the single SULT1A gene present in rodents is mainly expressed in liver. The food processing contaminants, 5-hydroxymethylfurfural (HMF) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are bioactivated by human SULT1A1 and SULT1A2. FVB multiple intestinal neoplasia (Min) mice, which spontaneously develop tumors and flat aberrant crypt foci (ACF) in intestine, were crossed with transgenic FVB mice expressing human SULT1A1 and 1A2 (hSULT) in several tissues, giving rise to wild-type and Min mice with and without hSULT. One-week-old Min mice with or without hSULT were given HMF (375 or 750 mg/kg bw) or saline by gavage three times a week for 11 wk. In another experiment, the F1 generation received subcutaneous injections of 50 mg/kg bw PhIP or saline 1 wk before birth, and 1, 2, and 3 wk after birth. HMF did not affect the formation of tumors, but may have induced some flat ACF (incidence 15-20%) in Min mice with and without hSULT. No control mouse developed any flat ACF. With the limitation that these putative effects were weak, they were unaffected by hSULT expression. The carcinogenic effect of PhIP increased in the presence of hSULT, with a significant increase in both incidence (31-80%) and number of colonic tumors (0.4-1.3 per animal). Thus, intestinal expression of human SULT1A1 and 1A2 might increase the susceptibility to compounds bioactivated via this pathway implying that humans might be more susceptible than conventional rodent models.

Topics: Animals; Carcinogens; Food Handling; Furaldehyde; Humans; Imidazoles; Intestinal Neoplasms; Mice; Mice, Transgenic; Sulfotransferases

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