title: Reporter gene mutation in the livers of gpt delta mice treated with 5-(hydroxymethyl)-2-furfural, a contaminant of various foods.
abstract: A major product formed during the Maillard reaction is 5-(hydroxymethyl)-2-furfural (HMF), which is present in various foods and beverages such as honey and fruit juice. HMF was shown to be a hepatocarcinogen in female mice using long-term bioassays. Although HMF is not a mutagen in conventional in vitro mutation assays, 5-sulfoxymethylfurfural (SMF), a reactive metabolite of HMF produced following sulfotransferase conjugation, does show mutagenicity. Thus, HMF-induced hepatocarcinogenesis likely involves genotoxic mechanisms. To clarify the mechanisms underlying HMF-induced hepatocarcinogenesis, female B6C3F(1) gpt delta mice were given HMF at carcinogenic doses (188 or  375 mg/kg b.w.) by gavage for 5 days per week for 4 weeks. This treatment produced no significant differences in mutant frequencies (MFs) of gpt and red/gam (Spi(-)) genes among the groups. These results suggest that genotoxicity does not contribute to HMF-induced hepatocarcinogenesis. Parameters related to cell proliferation, such as proliferation cell nuclear antigen-labeling index and Cyclin D1 and E1 mRNA expression, exhibited no significant changes in the livers of HMF-treated groups. In view of the lack of carcinogenicity in rats, HMF may be considered to be a weak carcinogen. These results help us to understand the underlying mechanisms of action of HMF carcinogenesis.
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsushita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Aki
authors.initials: A
authors.lastname: Kijima
authors.forename: Meilan
authors.initials: M
authors.lastname: Jin
authors.forename: Shinji
authors.initials: S
authors.lastname: Takasu
authors.forename: Ken
authors.initials: K
authors.lastname: Kuroda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kodama
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D019938:Cyclin D1 / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D005260:Female; D005506:Food Contamination; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D017930:Genes, Reporter; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D010430:Pentosyltransferases / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002273:Carcinogens; C530105:Ccnd1 protein, mouse; D019927:Cyclin E; D029968:Escherichia coli Proteins; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C568314:cyclin E1, mouse; D019938:Cyclin D1; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D010430:Pentosyltransferases; C071962:Gpt protein, E coli